Combination therapy

Abstract

The present disclosure provides immune cells comprising an exogenous T cell receptor (TCR) and T cell modulatory polypeptides (TMPs) for use in methods of treating a disease or condition. The TMPs comprise one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell. Also disclosed are methods of expanding a population of immune cells and methods of selectively delivering an immunomodulatory polypeptide using the same. Also disclosed are pharmaceutical combinations comprising the same and their use in methods of treating a disease or condition.

Description

Combination TherapyThis application claims priority from US 63 / 733749 filed 13 December 2024 and US 63 / 797,477 filed 30 April 2025, the contents and elements of which are herein incorporated by reference for all purposes.Technical FieldThe present disclosure relates to TCR-based immunotherapies.BackgroundIn 2022, there were an estimated 20 million new cancer cases and 9.7 million deaths. Despite significant advancements in treatments for certain malignancies, there remains a substantial unmet need for accessible, effective, and safe treatments for patients with solid tumors.While chemotherapy is the mainstay of treatment for solid cancers, responses in relapsed or refractory cases are frequently limited and curtailed by treatment-related toxicity. Over the past decade, advances in understanding the mechanisms underpinning anti-tumor activity in immune cells have led to the advent of adoptive cell therapy as a promising alternative to conventional chemotherapy. Ongoing research has led to the development of immune adoptive transfer of ex vivo expanded tumor infiltrating T cells, CAR-T cell therapy and TCR-T therapy.The binding domain of Chimeric antigen receptors (CARs) are based on antibody fragments that bind to unprocessed antigens, such as tumor antigens on the surface of tumor cells. Upon binding to a certain threshold number of target antigens displayed on the target cell, the CAR-expressing T cell can become activated and can kill the tumor cell.The binding mechanism of a T cell receptor (TCR) is entirely different from that of a CAR. A TCR is a natural component of T cells. Each TCR has a unique structure that is designed to ‘recognize,’ i.e., ‘specifically bind’ to, a fragment of a specific peptide (antigen fragment) bound to a Major Histocompatibility Complex (MHC) molecule on the surface of a cell. This specificity is due the unique variable regions of each TCR, which are generated through a recombination process during development of the T cell. The binding between the TCR and the peptide:MHC complex is highly specific, meaning that each TCR is designed to recognize a particular peptide presented by a specific MHC molecule, and the TCR can distinguish its target peptide from other similar molecules. This specificity ensures that T cells respond to the correct antigens, which is crucial for an effective immune response.Upon binding of potentially a single TCR with a single MHC class I molecule displaying the target peptide of the TCR, the first step of the T cell activation cascade is initiated. This exquisite sensitivity of TCR- mediated killing by T cells provides an opportunity to use these cells in adoptive T cell therapy for cancer, particularly in cases where the level of expression of the target antigen may be low. T cells can be genetically modified to equip them with an exogenous TCR specifically targeting a peptide that is processed from a tumor antigen and presented on the surface of a patient’s tumor in the context of a Human Leukocyte Antigen (HLA) molecule. An example of this modality is TECLERA®, which is a melanoma-associated antigen A4-(MAGE-A4)-directed genetically modified autologous T cell immunotherapy recently given FDA approval for treating adults with unresectable or metastatic synovialsarcoma and whose tumor expresses the MAGE-A4 antigen. TECLERA is administered in a dose of between 2.68 x 109to 10 x 1010cells. Alternatively, the TCRs can be used in other immunotherapeutic modalities, such as bi-specific molecules. An example of this modality is the marketed drug KIMMTRAK® that comprises a TCR specific for a gp100-derived peptide when presented in the context of HLA- A*02:01 , linked to a T cell engaging anti-CD3 binding domain.TCR-based therapies are based on the binding of TCRs to peptides presented in the context of MHC molecules (also referred to herein as ‘HLA molecules’). For a TCR-based therapy against cancer, the target antigens of the TCR must be expressed in tumor cells, and the patient must express the HLA allele to which the TCR is restricted. As part of immune presentation of antigens to CD8+ T cells, antigens are broken down into peptides by the proteasome or immunoproteasome, leading to the presentation of these peptides on MHC molecules. CD8+ T cells, via their TCR, bind to peptides presented on a given allele of MHC class I molecules. The specific binding of T cells to peptides presented by a given MHC class I molecule is called HLA restriction of the T cell response (Murphy & Weaver (2017) Janeway’s Immunobiology 9). Once a T cell has bound to the cancer cell via the TCR:MHC+peptide interaction and the cell is activated by additional stimuli, the T cell can kill the tumor cell.TCR-T cell therapies hold tremendous promise as strategies to target solid tumor indications. TCR-T cells recognize polypeptides derived from both tumor cell surfaces and intracellular compartments, allowing them to target a wide range of antigens. Ideally, the antigen should be expressed exclusively or predominantly on the tumor compared to normal healthy tissue. A key success factor for TCR-based therapies is the selection of the tumor antigen, such that as many patients as possible can benefit from a given therapy. Tumor antigens that are expressed in several tumor types and in a large proportion of patients (so-called shared tumor antigens) are therefore of high priority. A number of shared tumor antigens have been tested in TCR-T cell therapy clinical trials so far (Baulu et al., 2023, Science Advances, 9(7)). Alongside the recently approved TECLERA®, results from ongoing clinical trials with these few antigens have been very encouraging and further TCR-T therapies are likely to be approved for clinical use in the near future.Despite such tremendous promise, however, current TCR-T cell therapies also have some significant drawbacks. One drawback is that the number of TCR-T cells administered to patients is so large that patients can experience severe or life-threatening cytokine release syndrome. The large number of cells also necessitates that, prior to receiving the infusion of TCR-T cells, the patient must undergo a lymphodepletion regimen, e.g., with chemotherapeutics such as cyclophosphamide and fludarabine.Additionally, following administration, the number of the TCR-T cells (and thus their effectiveness) will decrease over time. Hence, TCR-T cell therapies may have only a limited period of effectiveness. Further, one possible method for prolonging the TCR-T cells in vivo is the administration to the patient of the recombinant IL-2 drug, aldesleukin (also known as Proleukin®). Adverse events with aldesleukin, however, are frequent, often serious, and sometimes fatal.Hence, there is a need for solutions to one or more of the above problems associated with current TCR-T therapies.SummaryProvided is an immune cell comprising a T cell receptor (TCR) capable of binding to an antigen for use in a method of treating a disease or condition, wherein the method comprises administering a T-cell modulatory polypeptide capable of binding to and activating the immune cell comprising the TCR.Also provided is a T-cell modulatory polypeptide for use in a method of treating a disease or condition, wherein the method comprises administering an immune cell comprising a T cell receptor (TCR) capable of binding to an antigen, and wherein the T-cell modulatory polypeptide is capable of binding to and activating the immune cell comprising the TCR.Also provided is use of an immune cell comprising a T cell receptor capable of binding to an antigen in the manufacture of a medicament for use in a method of treating a disease or condition, wherein the method comprises administering a T-cell modulatory polypeptide capable of binding to and activating the immune cell comprising the TCR.Also provided is use of a T-cell modulatory polypeptide in the manufacture of a medicament for use in a method of treating a disease or condition, wherein the method comprises administering an immune cell comprising a T cell receptor capable of binding to an antigen, and wherein the T-cell modulatory polypeptide is capable of binding to and activating the immune cell comprising the TCR.Also provided is a method of treating a disease or condition, comprising administering to a subject a therapeutically- or prophylactically-effective amount of (I) an immune cell comprising a T cell receptor capable of binding to an antigen and (II) a T-cell modulatory polypeptide capable of binding to and activating the immune cell comprising the TCR.In some embodiments, the method does not comprise administering a lymphodepleting chemotherapy to the subject prior to administration of the immune cell comprising a TCR.Also provided is a method of expanding a population of immune cells comprising an exogenous T cell receptor capable of binding to an antigen, the method comprising contacting in vitro or in vivo the population of immune cells with a T cell modulatory polypeptide capable of binding to and activating the immune cell comprising the TCR.Also provided is a method of delivering an immunomodulatory polypeptide to a target immune cell comprising an exogenous T cell receptor capable of binding an antigen, the method comprising contacting in vitro or in vivo, a mixed population of immune cells with a T-cell modulatory polypeptide, wherein the mixed population of immune cells comprises the target immune cell.Also provided is a pharmaceutical combination, comprising (I) an immune cell comprising a T cell receptor capable of binding to an antigen and (II) a T-cell modulatory polypeptide capable of binding to and activating the immune cell comprising the TCR.In some embodiments, the TCR is an exogenous TCR.In some embodiments, the TCR is capable of binding to a disease-associated antigen.In some embodiments, the TCR is capable of binding to a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from: WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , surviving, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1 R, prostate specific antigen, -catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF-0RII, MUC1 , heatshock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL- 2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.In some embodiments, the cancer-associated antigen is selected from: WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.In some embodiments, the TCR is capable of binding to an antigen-derived peptide.In some embodiments, the TCR is capable of binding to an antigen-derived peptide when presented by an MHC class I molecule, optionally an MHC molecule comprising an MHC class I a chain polypeptide.In some embodiments, the antigen-derived peptide comprises or consists of the amino acid sequence of: (I) SEQ ID NO:1 , 179, 180, 181 or 182, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele;(ii) SEQ ID NO:191 or 223, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele;(ill) SEQ ID NO:225 or 226, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele; or(iv) SEQ ID NO:227 or 228, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*24 allele, optionally a HLA-A*24:02 allele.In some embodiments, the TCR is capable of binding to antigen-derived peptide:MHC complex, optionally an antigen-derived peptide:MHC complex comprising an MHC class I a chain polypeptide.In some embodiments, the antigen-derived peptide comprises or consists of the amino acid sequence of:(i) SEQ ID N0:1 , 179, 180, 181 or 182, optionally wherein the MHC molecule comprises an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele;(ii) SEQ ID NO:191 or 223, optionally wherein the MHC molecule comprises an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele;(iii) SEQ ID NO:225 or 226, optionally wherein the MHC molecule comprises an MHC class I a chain polypeptide encoded by a HLA-A*02 allele, optionally a HLA-A*02:01 allele; or(iv) SEQ ID NO:227 or 228, optionally wherein MHC molecule comprises an MHC class I a chain polypeptide encoded by a HLA-A*24 allele, optionally a HLA-A*24:02 allele.In some embodiments, the TCR comprises:(a) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:34; in combination with (ii) a TCRfJ variable domain comprising a CDR3fJ having an amino acid sequence of SEQ ID NO:37;(b) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO: 10; in combination with (ii) a TCRfJ variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:13;(c) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:4; in combination with (ii) a TCR0 variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:7;(d) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO: 16; in combination with (ii) a TCRfJ variable domain comprising a CDR3fJ having an amino acid sequence of SEQ ID NO:19;(e) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:22; in combination with (ii) a TCRfJ variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:25;(f) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:28; in combination with (ii) a TCRfJ variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:31 ;(g) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NQ:40; in combination with (ii) a TCRfJ variable domain comprising a CDR3fJ having an amino acid sequence of SEQ ID NO:43;(h) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:46; in combination with (ii) a TCRfJ variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:49;(i) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO: 194; in combination with (ii) a TCRfJ variable domain comprising a CDR3fJ having an amino acid sequence of SEQ ID NO:197;(j) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:231 ; in combination with (ii) a TCRfJ variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:234;(k) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:237; in combination with (ii) a TCR variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:240;(l) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:243; in combination with (ii) a TCR0 variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:246;(m) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:249; in combination with (ii) a TCR0 variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:252;(n) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:255; in combination with (ii) a TCR0 variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:258;(o) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:261 ; in combination with (ii) a TCR0 variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:264; or(p) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:267; in combination with (ii) a TCR0 variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NQ:270.In some embodiments, the TCR comprises:(a)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:32 CDR2a having the amino acid sequence of SEQ ID NO:33 CDR3a having the amino acid sequence of SEQ ID NO:34, and / or(ii) a TCR0 chain variable domain incorporating the following CDRs:CDR10 having the amino acid sequence of SEQ ID NO:35 CDR20 having the amino acid sequence of SEQ ID NO:36 CDR30 having the amino acid sequence of SEQ ID NO:37;(b)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:8 CDR2a having the amino acid sequence of SEQ ID NO:9 CDR3a having the amino acid sequence of SEQ ID NQ:10, and / or(ii) a TCR0 chain variable domain incorporating the following CDRs:CDR10 having the amino acid sequence of SEQ ID NO:11 CDR20 having the amino acid sequence of SEQ ID NO:12 CDR30 having the amino acid sequence of SEQ ID NO:13;(c)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:2CDR2a having the amino acid sequence of SEQ ID NO:3CDR3a having the amino acid sequence of SEQ ID NO:4, and / or(ii) a TCRp chain variable domain incorporating the following CDRs: CDRip having the amino acid sequence of SEQ ID NO:5 CDR2P having the amino acid sequence of SEQ ID NO:6 CDR3P having the amino acid sequence of SEQ ID NO:7;(d)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:14 CDR2a having the amino acid sequence of SEQ ID NO:15 CDR3a having the amino acid sequence of SEQ ID NO:16, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:17 CDR2P having the amino acid sequence of SEQ ID NO:18 CDR3P having the amino acid sequence of SEQ ID NO: 19;(e)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NQ:20 CDR2a having the amino acid sequence of SEQ ID NO:21 CDR3a having the amino acid sequence of SEQ ID NO:22, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:23 CDR2P having the amino acid sequence of SEQ ID NO:24 CDR3P having the amino acid sequence of SEQ ID NO:25;(f)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:26 CDR2a having the amino acid sequence of SEQ ID NO:27 CDR3a having the amino acid sequence of SEQ ID NO:28, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:29 CDR2P having the amino acid sequence of SEQ ID NQ:30 CDR3P having the amino acid sequence of SEQ ID NO:31 ;(g)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:38 CDR2a having the amino acid sequence of SEQ ID NO:39 CDR3a having the amino acid sequence of SEQ ID NQ:40, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:41 CDR2P having the amino acid sequence of SEQ ID NO:42 CDR3P having the amino acid sequence of SEQ ID NO:43;(h)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:44 CDR2a having the amino acid sequence of SEQ ID NO:45 CDR3a having the amino acid sequence of SEQ ID NO:46, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:47 CDR2P having the amino acid sequence of SEQ ID NO:48 CDR3P having the amino acid sequence of SEQ ID NO:49;(i)(I) a TCRa chain variable domain incorporating the following CDRs: CDR1a having the amino acid sequence of SEQ ID NO: 192 CDR2a having the amino acid sequence of SEQ ID NO: 193 CDR3a having the amino acid sequence of SEQ ID NO: 194, and / or(ii) a TCRp chain variable domain incorporating the following CDRs: CDRip having the amino acid sequence of SEQ ID NO: 195 CDR2P having the amino acid sequence of SEQ ID NO: 196 CDR3P having the amino acid sequence of SEQ ID NO:197;0)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:229 CDR2a having the amino acid sequence of SEQ ID NO:230 CDR3a having the amino acid sequence of SEQ ID NO:231 , and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:232 CDR2P having the amino acid sequence of SEQ ID NO:233 CDR3P having the amino acid sequence of SEQ ID NO:234;(k)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:235 CDR2a having the amino acid sequence of SEQ ID NO:236 CDR3a having the amino acid sequence of SEQ ID NO:237, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:238 CDR2P having the amino acid sequence of SEQ ID NO:239 CDR3P having the amino acid sequence of SEQ ID NQ:240;(l)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:241 CDR2a having the amino acid sequence of SEQ ID NO:242 CDR3a having the amino acid sequence of SEQ ID NO:243, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:244CDR2 having the amino acid sequence of SEQ ID NO:245CDR3p having the amino acid sequence of SEQ ID NO:246;(m)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:247 CDR2a having the amino acid sequence of SEQ ID NO:248CDR3a having the amino acid sequence of SEQ ID NO:249, and / or(ii) a TCR chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NQ:250 CDR2 having the amino acid sequence of SEQ ID NO:251 CDR3P having the amino acid sequence of SEQ ID NO:252;(n)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:253 CDR2a having the amino acid sequence of SEQ ID NO:254CDR3a having the amino acid sequence of SEQ ID NO:255, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NO:256 CDR2 having the amino acid sequence of SEQ ID NO:257 CDR3 having the amino acid sequence of SEQ ID NO:258;(o)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:259 CDR2a having the amino acid sequence of SEQ ID NO:260CDR3a having the amino acid sequence of SEQ ID NO:261 , and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NO:262 CDR2 having the amino acid sequence of SEQ ID NO:263 CDR3 having the amino acid sequence of SEQ ID NO:264; or(P)(I) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:265 CDR2a having the amino acid sequence of SEQ ID NO:266CDR3a having the amino acid sequence of SEQ ID NO:267, and / or(ii) a TCRP chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NO:268 CDR2P having the amino acid sequence of SEQ ID NO:269 CDR3P having the amino acid sequence of SEQ ID NQ:270.In some embodiments, the TCR comprises:(a) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NQ:60; in combination with (ii) a TCR variable domaincomprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:61 ;(b) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:52; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:53;(c) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:50; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:51 ;(d) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:54; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:55;(e) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:56; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:57;(f) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:58; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:59;(g) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:62; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:63;(h) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:64; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:65;(i) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:198; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:199;(j) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:271; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:272;(k) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:273; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:274;(l) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:275; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:276;(m) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:277; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:278;(n) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:279; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NQ:280;(o) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:281; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:282; or(p) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:283; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:284.In some embodiments, the TMP comprises (i) a peptide:MHC complex that specifically binds to the TCR, and / or (ii) one or more immunomodulatory polypeptides.In some embodiments, the TMP comprises: i) a peptide epitope; ii) a first major histocompatibility complex (MHC) class I polypeptide, optionally wherein the first MHC class I polypeptide is a 02-microglobulin (02M) polypeptide; ill) one or more immunomodulatory polypeptides; iv) a second MHC class I polypeptide, optionally wherein the second MHC class I polypeptide is a MHC class I heavy chain polypeptide; and v) a scaffold polypeptide, optionally an immunoglobulin (Ig) Fc polypeptide, and wherein the TMP presents a peptide:MHC complex comprising the MHC class I polypeptides and the peptide epitope, and optionally wherein the TMP comprises one or more independently selected peptide linkers between any two of the component polypeptides, and optionally wherein when the TMP comprises more than one immunomodulatory polypeptide, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.In some embodiments, the peptide / peptide epitope is an epitope of a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1R, prostate specific antigen, |3-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF-|3RII, MUC1, heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.In some embodiments, the peptide / peptide epitope is an epitope of a cancer-associated antigen selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.In some embodiments, the peptide / peptide epitope comprises or consists of VLDFAPPGA (SEQ ID NO:1 ).In some embodiments, the TMP comprises a heterodimer comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO:422, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:423.In some embodiments, the TMP is a dimeric TMP (a DTMP).In some embodiments, the disease or condition is characterised by expression of the antigen.In some embodiments, the disease or condition is characterised by expression of an antigen selected from: WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, and PRAME.In some embodiments, the disease or condition is cancer or a neoplasm.In some embodiments, the disease or condition is selected from a solid cancer, WT-1 -expressing cancer, MAGE-A1 -expressing cancer, MAGE-A10-expressing cancer, MAGE-A4-expressing cancer, PRAME- expressing cancer, hematological cancer, gastric cancer (e.g., gastric carcinoma, gastric adenocarcinoma, gastrointestinal cancer, gastrointestinal adenocarcinoma), liver cancer (hepatocellular carcinoma, cholangiocarcinoma), head and neck cancer (e.g., head and neck squamous cell carcinoma), oral cavity cancer (e.g., oropharyngeal cancer (e.g., oropharyngeal carcinoma), oral cancer, oral squamous cell carcinoma (OSCC), laryngeal cancer, nasopharyngeal carcinoma, oesophageal cancer), colorectal cancer (e.g., colorectal carcinoma), colon cancer, colon carcinoma, cervical carcinoma, prostate cancer, lung cancer (e.g., NSCLC, small cell lung cancer, lung adenocarcinoma, squamous lung cell carcinoma), bladder cancer, urothelial carcinoma, urogenital cancer, skin cancer (e.g., melanoma, advanced melanoma), renal cell cancer (e.g., renal cell carcinoma), ovarian cancer (e.g., ovarian carcinoma), mesothelioma, breast cancer, brain cancer (e.g., glioblastoma), prostate cancer, pancreatic cancer, a myeloid hematologic malignancy, a lymphoblastic hematologic malignancy, myelodysplasticsyndrome (MDS), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), lymphoma, non-Hodgkin’s lymphoma (NHL), thymoma and multiple myeloma (MM).Brief Description of the FiguresEmbodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures.Figures 1A to 1F. Functional validation of WT-1 specific TCRs. (1A, 1 B) Graphs showing functional activation of Jurkat reporter cells transduced with WT-1 specific TCRs and exposed to target cells pulsed with a range of concentrations of WT-137-45 (SEQ ID NO:1 ). Estimated EC50 values are shown. (1C, 1 D) Graphs showing functional activation of Jurkat reporter cells electroporated with mRNA for WT-1 specific TCRs and exposed to target cells pulsed with a range of concentrations of WT-I37-45 (SEQ ID NO:1 ). Estimated EC50 values are shown. (1 E) Graph showing T cell activation as measured through levels of IFNy secretion. Primary T cells transduced with WT-1 specific TCRs were exposed to target cells pulsed with a range of concentrations of WT-137-45 (SEQ ID NO:1 ). Culture supernatants were then analysed for levels of IFNy with non-transduced T cells from the same donor serving as baseline adjustment.Figures 2A to 2F. Cytotoxic activity of primary T cells transduced with WT-1 specific TCRs. (2A) Graphs showing direct cytotoxic activity of primary T cells transduced with WT-1 specific TCRs as measured via flow cytometric quantification of CTV-stained target cells pulsed with a range of concentrations of WT-I37-45 (SEQ ID NO:1 ). Experiments were carried out at an E:T ratio of 1 :1 with nontransduced T cells from the same donor indicating background levels of cytotoxicity. (2B, 2C, 2D) Graphs showing IFNy secretion as a measure of cytotoxic activity of primary T cells transduced with TCR_A0431 against endogenous levels of WT-137-45 (SEQ ID NO:1 ) in CML cell line (K562 + HLA-A*02:01 ), ovarian cancer cell line (COV434 + HLA-A*02:01 ) and glioblastoma cell line (SF539). Experiments were carried out at 3 different E:T ratios of 0.3:1 , 1 :1 and 3:1 with means and standard deviations shown from duplicate measurements, except for single-measurements in non-transduced (NT) cell controls. ****p < 0.0001 ; two-way ANOVA followed by Sidak’s multiple comparisons test. (2E, 2F) Graphs showing results for xCELLigence technology as used to measure specific killing of cancer cell lines expressing endogenous levels of WT-137-45 and HLA-A*02:01 by primary T cells transduced with TCR_A0427 or TCR_A0431 over a period of 150 hours. Data shown are for two E:T ratio, 1 :1 and 3:1 , in the context of a ovarian cancer cell line (COV434 + HLA-A*02:01 ) or glioblastoma cell line (SF539). Non-transduced primary T cells from the same donor serve as negative control while Tween-20 treatment was a positive control for complete cell lysis.Figures 3A to 3H. Alanine scan and safety assessment for potential binding of TCRs to endogenous proteins. (3A, 3B, 3C, 3D, 3E) Graphs showing alanine scan of TCR A0418 (control), TCR A0427, TCR_A0429, TCR_A0431 and TCR_A0432 for target peptide, WT-137-45 (SEQ ID NO:1 ). Raji cells expressing HLA-A*02:01 were pulsed with EC90 levels of WT-I 37-45 (SEQ ID NO:1 ) carrying single alanine-substitutions at indicated positions (SEQ ID NO:172, 173, 174, 175, 176, 177 and 178). Primary T cells transduced with WT-1 specific TCRs were introduced at a 1 :1 ratio and T cell activation was measured through levels of IFNy secretion. Means and standard deviations from duplicatemeasurements were shown with values adjusted against no-peptide, non-transduced controls. (3F, 3G, 3H) Graphs showing potential alloreactivity of WT-1 specific TCRs, TCR A0427 and TCR_A0431 , was assessed against a panel of 35 LCL lines representing 73 unique HLA alleles, including 10 of the most frequent HLA-A,B,C in North America, Europe, and Northeast Asia. Each TCR was evaluated in two different primary T cell donors (donor A or B) where T cell activation was measured through levels of IFNy secretion. Means and standard deviations from duplicate measurements were shown with values adjusted against non-transduced T cell controls.Figures 4A and 4B. Functional validation of MAGE-A1 -specific TCR. Jurkat reporter cells transduced with (4A) TCR A0360, or (4B) TCR A0387 (codon-optimized version of TCR A0360), were contacted with HLA-A*02:01 -expressing Raji cells. A range of peptide concentrations as indicated on the x-axis were tested to verify dose-dependent T cell activation of Jurkat cells expressing MAGE-A1 -specific TCRs. Non-transduced (NT) Jurkat cells were used as a control.Figure 5. Cytotoxic activity of primary cells transduced with TCR A0387. Peptide KVLEYVIKV (SEQ ID NO:1 ) was added to peptide pulsed Raji HLA-A*02:01 target cells in a range of concentrations as indicated on the x-axis. A0387 TCR-expressing primary effector T cells were added at Effector to Target ratios (E:T) of 1:1 or 3:1. IFNy secretion was used to measure T cell activation. The estimated EC50 values for A0387_1 :1 and A0387_3:1 are shown.Figure 6. Cytotoxic activity of primary cells transduced with TCR A0387 using target cell lines endogenously expressing MAGE-A1. Target cell lines U266B1 and K562 expressing MAGE-A1 were tested from two different donors (A and B). K562 cells were optionally transduced with HLA-A*02:01 . Effector cells expressing TCR A0387 were added to target cells in a 1 :1 or 3:1 Effector:Target ratio (E:T). Bars show means±SD of duplicates. NT: non-transduced controls.Figure 7. Alanine scan for target peptide of TCR A0387. Each amino acid of peptide KVLEYVIKV (SEQ ID NO:1 ) was replaced in turn by an alanine (A) and individual mutated peptides were used to generate Raji-A*02:01 target cells. Primary effector cells were obtained from two different donors (A and B) and transduced with TCR A0387. Each graph shows data for one donor (left graph for donor A, right graph for donor B). Bars show means±SD of duplicates.Figures 8A to 8E. Continuous killing activity measurement over several days with TCR A0387. xCelligence technology was used to measure killing activity of A0387-transduced primary T cells against cell lines that endogenously express MAGE-A1 . (8A) Cytotoxicity against lung cell line EKVX. Target cells EKVX were optionally transduced with HLA-A*02:01 (EKVX*02). Two different effector to target ratios (E:T) were used, 1 :1 and 3:1. NT: non-transduced. (8B) Cytotoxicity against HLA-A*02:01 positive melanoma cell line UACC-62 at 1 :1 E:T for donor A and donor B. NT: non-transduced. (8C) Cytotoxicity against HLA-A*02:01 positive melanoma cell line UACC-257 at 1 :1 E:T for donor A and donor B. (8D and 8E) Cytotoxicity against HLA-A*02:01 positive lung carcinoma cell line NCI-H1299 at 1 :1 E:T for (D) donor A and (E) donor B. NCI-H1299 cells were optionally transduced with HLA-A*02:01 (NCI-H1299-A*02). NT: non-transduced controls.Figures 9A and 9B Binding of TCR A0387 to human proteins containing a peptide with the motif KX1X2EX3VIX4X5 wherein each of Xi, X2, X3, X4 and X5 can be any amino acid. The top 50 ranked peptides predicted to bind to HLA-A*02:01 were tested using TCR-transduced primary T cells from two different donors (donor A in 9A, donor B in 9B) as effectors. IFNy production was used as a readout. X- axis indicates peptides that were tested.Figures 10A and 10B. Alloreactivity of TCR A0387. IFNy secretion of primary T cells transduced with (10A) TCR A0387 or (10B) competitor TCR A0010 after incubation with 35 target cells with HLA-A,B,C expression that covers the most frequent HLA-A,B,C alleles in North America, Europe, and Northeast Asia. The arrow indicates EBV-LCL NO 18 for which potential alloreactivity of TCR A0010 was observed. NT: non-transduced. LOD: Limit of detection.Figures 11A to 11C. Functional validation of MAGE-A10-specific TCRs. (A) Binding of Jurkat reporter TCR-knockout cells transduced with TCR A0385 (JR A0385) to a range of concentrations of MAGE-A10 peptide GLYDGMEHL (SEQ ID NO:225) (0.000005 - 5 pM, 10-fold dilutions). (B). Binding of Jurkat cells transduced (lentiviral) with TCR A0390 (A0390) and TCR A0398 (A0398) to a range of concentrations of MAGE-A10 peptide SLLKFLAKV (SEQ ID NO:226) (0.000005 - 5 pM, 10-fold dilutions). (C) Comparative binding of Jurkat cells electroporated (mRNA) with TCR A0409 (A0409) or TCR A0436 (A0436) to a range of concentrations of MAGE-A10 peptide SLLKFLAKV (SEQ ID NO:226) (0.000005 - 5 pM, 10-fold dilutions). (JR: Jurkat reporter TCR-KO cells; NT: Non-transduced Jurkat cells used as a negative control.Figure 12. Peptide-specific cytokine secretion by primary T cells transduced with TCR A0385 and TCR A0409. Peptides SLLKFLAKV (SEQ ID NO:226) or GLYDGMEHL (SEQ ID NO:225) were added to peptide pulsed HLA-A*02:01 target cells in a range of concentrations indicated on the x-axis. A0385 TCR-expressing or A0409 TCR-expressing primary effector T cells were added at Effector to Target (E:T) ratios of 1 :1 . IFNy production was used to measure T cell activation. The estimated EC50 values for A0385 and A0409 are shown. Non-transduced (NT) cells were used as a control.Figure 13. Cytotoxic activity of primary T cells transduced with TCR A0409. Primary human T cells transfected with TCR A0409 (specific for MAGE-A10 peptide SLLKFLAKV (SEQ ID NO:226)) were used as effector (E) cells. The cell viability index represents the ratio of peptide pulsed versus un-pulsed Raji- A*02 target (T) cells. Three E:T ratios, 1 :1 , 2:1 and 6:1 , were tested in duplicate. An un-pulsed control condition was used for normalization (not tested in duplicate). The graph shows mean and range of the two measurements per condition except for the no-peptide control which is a single measurement. Nontransduced (NT) cells were used as a control.Figures 14A to 14F. Cytotoxic activity of primary cells transduced with TCR A0385 against target cells expressing MAGE-A10. The following target cell lines expressing MAGE-A10 were tested from two different donors (A and B): (14A, 14B) EKVX cells, optionally transduced with HLA-A*02:01 ; (14C, 14D) SK-MEL-2 cells, optionally transduced with HLA-A*02:01 (3C-3D); (14E, 14F) A375 cells thatendogenously express HLA-A*02:01 . Effector cells expressing TCR A0385 were added to target cells at Effector to Target (E:T) ratios indicated in the Figures. IFNy production was used to measure T cell activation. Non-transduced (NT) cells were used as a control.Figures 15A to 15F. Cytotoxic activity of primary cells transduced with TCR A0390 and A0398 using target cells expressing MAGE-A10. The following target cell lines expressing MAGE-A10 were tested: (15A, 15D) EKVX cells, optionally transduced with HLA-A*02:01 ; (15B, 15E) SK-MEL-2 cells, optionally transduced with HLA-A*02:01 ; and (15C, 5F) A375 cells that endogenously express HLA- A*02:01 . Effector cells from donor A expressing TCR A0390 (15A, 15B, 15C) and TCR A0398 (15D, 15F) were added to target cells at Effector to Target (E:T) ratios indicated in the Figures. IFNy production was used to measure T cell activation. Non-transduced (NT) cells were used as a control.Figure 16. Continuous killing activity measurement over 140 hours with primary cells transduced with TCR A0390 and A0398. xCelligence technology was used to measure killing activity of TCR A0390-transduced or TCR A0398-transduced primary T cells against cell lines which express MAGE-A10 peptides. Cytotoxicity against melanoma cell line SK-MEL2, optionally transduced with HLA-A*02:01 , was measured at an Effector to Target (E:T) ratio of 3:1 . Non-transduced (NT) cells were used as a control.Figures 17A to 17G. (17A, 17B) Immuno-STATs (ISTs) selectively and greatly expand MAGE-A1- specific TCR-T cells in vitro. MAGE-A1 TCR transduced primary T cells were spiked into a total of 1 .5M autologous PBMCs at 1% and incubated in the presence of MAGE-A1 peptide (KVLEYVIKV) loaded ISTs (IST-4951-001 (MAGE-A-1)) at 1-300nM or irrelevant CMVpp65 peptide (NLVPMVATV) loaded ISTs (IST-1715-1717-016 (CMV)) at 1-300 nM. MAGE-A1 peptide with rlL-2, CMVpp65 peptide with rlL-2 and media only served as controls. Expansion of MAGE-A1 TCR-T cells was analyzed after 8 days as (A) percentage of total CD8+ T cells in the culture and (B) as total MAGE-A1 TCR-T cell numbers in the cell culture. (17C, 17D, 17E, 17F) Immuno-STATs selectively and greatly expand WT1 -specific TCR-T cells in vitro. WT 1 TCR (A0427 and A0431 ) transduced primary T cells were spiked into a total of 1 .5M autologous PBMCs at 1% and incubated in the presence of WT-137-45 peptide loaded ISTs (CUE-102- C001-R005-DS001-DP-001 WT1 ) at 1-300nM, or irrelevant MAGE-A1278-286 peptide (KVLEYVIKV) loaded ISTs (IST-4951-001 (MAGE-A-1 )) at 1-300 nM. MAGE-A1278-286 peptide with rlL-2, WT-137-45 peptide with rlL-2 and media only served as controls. Expansion of WT1 (A0427) TCR-T cells was analyzed after 8 days as (C) percentage of total CD8+ T cells in the culture and (D) as total MAGE-A1 TCR-T cell numbers in the cell culture. Expansion of WT1 (A0431 ) TCR-T cells was analyzed after 8 days as (E) percentage of total CD8+ T cells in the culture and (F) as total MAGE-A1 TCR-T cell numbers in the cell culture. (17G) Immuno-STATs specifically expand MAGE-A1 TCR-T and WT-1 TCR-T cells in vitro. WT1 TCR (A0431 ) and MAGE-A1 transduced primary T cells were spiked together into a total of 1.5M autologous PBMCs at 1% and incubated in the presence of WT-137-45 peptide loaded ISTs (CUE- 102-C001-R005-DS001 -DP-001 WT1 ) at 1-300nM and MAGE-A1278-286 peptide (KVLEYVIKV) loaded ISTs (IST-4951-001 (MAGE-A-1 )) at 1-300 nM. MAGE-A1278-286 peptide with rlL-2, WT-137-45 peptide with rlL-2 and media only served as controls. Expansion of WT1 (A0431 ) and MAGE-A1 TCR-T cells was analyzed after 8 days as percentage of total CD8+ T cells in the culture.Figures 18A to 18D. (18A, 18B) Immuno-STATs greatly expand MAGE-A1 TCR-T cells in vivo. A total of 15M MAGE-A1 TCR transduced primary T cells was transferred into NSG mice and MAGE-A1278-286 peptide (KVLEYVIKV) loaded ISTs were administered 4h and 21 days post cell transfer. MAGE-A1 TCR- T cells alone and PBS (vehicle) served as controls. MAGE-A1 TCR-T cells were analyzed in blood (A) as percentage of CD3 positive cells of total live cells at day 4, 11 , 21 (prior 1ST dosing), and day 28 post cell transfer and (B) as total number of human CD3 positive cells per ml blood 28 days post cell transfer. (18C, 18D) Immuno-STATs selectively expand MAGE-A1 TCR-T cells in vivo. A total of 5M and 15M MAGE-A1 transduced primary T cells was transferred into NSG mice and MAGE-A1278-286 peptide (KVLEYVIKV) loaded ISTs were administered 4h and 21 days post cell transfer. MAGE-A1 TCR-T cells alone, MAGE-A1 TCR-T cells in combination with CMVpp65 peptide (NLVPMVATV) loaded ISTs, nontransduced T cells (NT) and PBS (vehicle) served as controls. (C) MAGE-A1 TCR-T cells were analyzed as total number of human CD3 positive cells (top) and VB9.01 positive cells (bottom) per ml blood 28 days post cell transfer. (D) MAGE-A1 TCR-T cells were analyzed as total number of CD3 positive cells per spleen 28 days post transfer of 15M (top) and 5M (bottom) MAGE-A1 TCR-T cells.Figures 19A to 19B. (19A) Immuno-STATs greatly expand WT1 TCR-T cells in vivo. A total of 15M WT1 TCR (A0431 ) transduced primary T cells was transferred into NSG mice and WT-137-45 peptide loaded ISTs (CUE-102) were administered 4h, 7 days, 14 days, and 21 days post cell transfer. WT1 TCR-T cells alone and non-transduced T cells (NT) alone and in combination with CUE-102 served as controls. WT-1 TCR-T cell and NT cell numbers were analysed in blood at day 14 as human CD3 positive cells and displayed as percent fold change between groups receiving CUE-102 and groups receiving TCR-T and NT cell alone, respectively. (19B) Immuno-STATs shift CD4 to CD8 WT-1 TCR-T cell ratio towards higher numbers of CD8 positive WT 1 TCR-T cells. A total of 15M WT 1 TCR (A0431 ) transduced primary T cells was transferred into NSG mice and WT-137-45 peptide loaded ISTs (CUE-102) were administered 4h, 7 days, 14 days, and 21 days post cell transfer. WT1 TCR-T cells alone served as controls. CD4 positive and CD8 positive WT-1 TCR-T cell numbers were analysed in blood at day 14 as percentage of human CD3 CD4 positive cells and human CD3 CD8 positive T cells of total live cells.Figures 20A to 20C. Immuno-STAT dosing over time maintains and greatly increases WT1 TCR-T cell numbers in vivo A total of 15M WT 1 TCR (A0431 ) transduced primary T cells was transferred into NSG mice and two different concentrations of WT-137-45 peptide loaded ISTs (CUE-102) were administered 4h, 7 days, 14 days, and 21 days post cell transfer. WT1 TCR-T cells alone and non-transduced T cell served as controls. WT-1 TCR-T cell numbers were analysed (20A) in blood at day 14 and day 28 as human CD3 positive cells per l blood, (20B) in blood as percent fold change between day 14 and day 28 in groups receiving 3mg / kg CUE-102 and 30mg / kg CUE-102 respectively and (20C) at day 28 in spleens of mice receiving WT-1 TCR-T cells alone or in combination with 3mg / kg CUE-102 or 30mg / kg CUE-102, respectively.Figures 21 A to 21 D. In vitro cytotoxicity of TCR T cells in combination with CUE-102 against ovarian cancer cells. (21 A, 21 B, 21 C) xCELLigence technology was used to measure specific killing of ovarian cancer cells, COV434 + HLA-A*02:01 , by primary T cells from 3 donors transduced with TCR A0431 over a period of 150 hours. CUE-102 was added in combination with TCR T at final concentrations of 5, 20and 100nM. Data shown are for the indicated E:T ratio of 1 :10. Non-transduced primary T cells from the same donor served as the negative controls. (21 D) Flow cytometric analysis was used to enumerate effector T cells in each condition at the end of the study. Cells we collected and stained for T-cell specific markers and TCR V 8 before enumeration on a flow cytometer using standardized counting beads. T cells, both CD4+ and CD8+, transduced with TCR A0431 but not NT, were observed to have proliferated in a dose-dependent manner in the presence of CUE-102. Data shown represent samples from all 3 donors tested.Figures 22A to 22F. Anti-tumor efficacy of TCR A0431 T cells and CUE-102 combination therapy in a mouse model of human ovarian cancer. (22A) Study plan to evaluate in-vivo efficacy of TCR A0431 T cells) and CUE-102 combination therapy. (22B, 22C) Tumor fold change and tumor volume after treatment with CUE-102 only, varying doses of TCR A0431 T cells alone or varying doses of TCR A0431 T cells in combination with CUE-102. (22D) TCR A0431 T cells detected in the peripheral blood of mice just before each weekly CUE-102 dosing. (22E) t-SNE analysis examining for differential phenotypic expression of tumor-infiltrating TCR A0431 T cells induced by the co-administration of CUE-102. (22F) PD-1 expression in tumor-infiltrating TCR A0431 T cells from mice which received TCR A0431 T cells alone or in combination with CUE-102.Figures 23A to 23C. Anti-tumor efficacy of TCR A0431 T cells and CUE-102 combination therapy in a mouse model of pancreatic cancer. (23A) Fold change in tumor volume after treatment with CUE-102 only (1ST), TCR A0431 T cells alone (TCR-T) or TCR A0431 T cells in combination with CUE-102 (TCR-T + CUE-102. (23B) Images showing T cell infiltration in mice treated with CUE-102 alone, TCR A0431 T cells alone or TCR A0431 T cells in combination with CUE-102 at day 6, day 9 and day 13 post T cell administration. (23C) Graph showing average radiance in tumors in mice treated with CUE-102 only, TCR A0431 T cells only or TCR A0431 T cells in combination with CUE-102.Figures 24A to 24D. Anti-tumor efficacy of TCR A0431 T cells and CUE-102 combination therapy in a mouse model of ovarian cancer. (24A) Tumor volume in mice treated with CUE-102 only, TCR A0431 T cells only or TCR A0431 T cells in combination with CUE-102. (24B) % survival of mice treated with CUE- 102 only, TCR A0431 T cells only or TCR A0431 T cells in combination with CUE-102. (23C) TCR A0431 T cells detected in the peripheral blood of mice treated with TCR A0431 only or TCR A0431 T cells in combination with CUE-102. (24D) Ratio of CD4 T cells to CD8 T cells in the peripheral blood of mice treated with TCR A0431 only or TCR A0431 T cells in combination with CUE-102.Figures 25A and 25B. Anti-tumor efficacy of TCR A0431 T cells and CUE-102 combination therapy in a mouse model of acute myeloid leukaemia (AML). (25A, 25B) Tumor burden as showed by average radiance in untreated mice or mice treated with varying doses of TCR A0431 T cells alone or varying doses of TCR A0431 T cells in combination with CUE-102.DescriptionCells comprisinq / expressinq TCRsThe present disclosure provides a cell, or a plural ity / popu lation of cells, comprising / expressing antigenbinding molecules, e.g., T cell receptors (TCRs), e.g., exogenous TCRs. The cel l / cells may express or comprise an antigen-binding molecule, e.g., TCR or fragment / chain thereof, according to the present disclosure. The cell / cel Is may comprise or express nucleic acid encoding an antigen-binding molecule, e.g., TCR or fragment / chain thereof, according to the present disclosure. Such cells may be called TCR- expressing cells. It will be appreciated that a TCR-expressing cell comprises the TCR it expresses. It will also be appreciated that a cell expressing nucleic acid encoding a TCR also expresses and comprises the TCR encoded by the nucleic acid. The cell / cells may express or comprise an antigen-binding molecule, e.g., TCR or fragment / chain thereof, according to the present disclosure on the surface of the cell.Aspects and embodiments of the present disclosure relate to host cells, and in particular immune cells. It will be appreciated that where cells are referred to herein in the singular ( / .e., ‘a / the cell’), a plurality / population of such cells is also contemplated.In aspects and embodiments of the present disclosure, the cells are primary cells. That is, in some embodiments, the cells are / were isolated directly from living tissue / a living subject. The cells may be from any animal or human. The cells may be mammalian, more preferably human. The cells may be from a human patient.In preferred embodiments, the host cell is an immune cell. An ‘immune cell’ may be a cell of hematopoietic origin, e.g., a neutrophil, eosinophil, basophil, dendritic cell, lymphocyte, or monocyte. A lymphocyte may be e.g., a T cell, B cell, NK cell, NKT cell or innate lymphoid cell (ILC), or a precursor thereof. The host cell / immune cell may express e.g., CD3 polypeptides (e.g., CD3y CD3E CD3 or CD35), TCR polypeptides (TCRa or TCRP), CD27, CD28, CD4 or CD8. In some embodiments, the host cell / immune cell is a T cell, e.g., a CD3+ T cell. In some embodiments, the T cell is a CD3+, CD4+ T cell. In some embodiments, the T cell is a CD3+, CD8+ T cell. In some embodiments, the T cell is a T helper cell (TH cell). In some embodiments, the T cell is a cytotoxic T cell (e.g., a cytotoxic T lymphocyte (CTL)).In some embodiments, the immune cell is an antigen-specific T cell. In some embodiments, the antigenspecific T cell is specific to an antigen described herein. An antigen-specific T cell may display certain functional properties of a T cell in response to the antigen / antigenic peptide for which the T cell is specific, or in response to a cell comprising / expressing the antigen / antigenic peptide. In some embodiments, the properties are functional properties associated with effector T cells, e.g., cytotoxic T lymphocytes (CTLs).In some embodiments, an antigen-specific T cell may display one or more of the following properties: cytotoxicity to a cell comprising / expressing the antigen / peptide thereof for which the T cell is specific; proliferation, IFNy expression, CD107a expression, IL-2 expression, TNFa expression, perforin expression, granzyme expression, granulysin expression, and / or FAS ligand (FASL) expression in response to stimulation with the antigen / peptide thereof for which the T cell is specific, or in response to exposure to a cell comprising / expressing the antigen / peptide thereof for which the T cell is specific.Antigen-specific T cells according to the present disclosure express / comprise an antigen-binding molecule / TCR / fragment thereof that is capable of recognizing a peptide of the antigen for which the T cell is specific when presented by the appropriate MHC molecule. In some embodiments, the antigen-specific immune cell is a T cell, e.g., a CD3+ T cell. In some embodiments, the T cell is a CD3+, CD4+ T cell. In some embodiments, the T cell is a CD3+, CD8+ T cell. In some embodiments, the T cell is a T helper cell (TH cell)). In some embodiments, the T cell is a cytotoxic T cell (e.g., a cytotoxic T lymphocyte (CTL)).In some embodiments, immune cells orT cells, according to the present disclosure are ‘engineered cells’ or ‘genetically engineered cells’. As used herein, an ‘engineered cell’ refers to a cell, e.g., immune cell / T cell, that has been genetically modified as compared to a naturally-occurring cell. The term ‘genetically engineered’ or ‘engineered’ refers to a method of modifying the genome of a cell, including, but not limited to, deleting a coding or non-coding region or a portion thereof or inserting a coding region or a portion thereof. In some embodiments, the cell that is modified is a lymphocyte, e.g., a T cell or a modified cell that expresses CD3, which can either be obtained from a patient or a donor. The cell can be modified (e.g., as described herein) to express an exogenous construct, such as, e.g., an antigen-binding molecule / TCR disclosed herein, which can be incorporated into the cell's genome. Any of the antigenbinding molecules / TCRs disclosed herein may be ‘exogenous’ antigen-binding molecules / TCRs with respect to the immune cell they are expressed in. As used herein an ‘exogenous’ antigen-binding molecule / TCR is an antigen-binding molecule / TCR that has been introduced into a given immune cell from an external source. In other words, exogenous antigen-binding molecules / TCRs are foreign to the immune cells (e.g., T cells) that are engineered to express them.In some embodiments, the cell is modified to express CD3. In some embodiments, the cell is modified to comprise / express an antigen-binding molecule, e.g., a TCR, according to the present disclosure. In some embodiments, the cell is modified to comprise / express a T cell receptor (TCR) capable of binding to an antigen (e.g., an antigen according to the present disclosure). In some embodiments, the cell is modified to comprise / express a T cell receptor (TCR) that binds to an antigen (e.g., an antigen according to the present disclosure). In some embodiments, the cell is modified to comprise / express a nucleic acid / vector encoding an antigen-binding molecule, e.g., a TCR, according to the present disclosure. T cells which have been engineered to express a TCR capable of binding to an antigen may be referred to as 'TCR- engineered T cells’ or ‘TCR-Ts’.In some embodiments, the immune cell does not comprise / express a chimeric antigen receptor (CAR). That is, in some embodiments, the immune cell comprises / expresses a TCR (e.g., a TCR capable of binding to an antigen) and does not comprise / express a chimeric antigen receptor (CAR). In some embodiments, the immune cell has not been modified to comprise / express a chimeric antigen receptor (CAR). That is, in some embodiments, the immune cell comprises / expresses and / or has been modified to comprise / express a TCR (e.g., a TCR capable of binding to an antigen) and has not been modified to comprise / express a chimeric antigen receptor (CAR).Any host / immune / T cell provided herein may be provided in a ‘purified’, ‘substantially purified’ or ‘isolated’ form. As used herein, a ‘substantially purified’ cell is a cell that is essentially free of other cell types. A substantially purified cell also refers to a cell which has been separated from other cell types with which it is normally associated in its naturally occurring state. In some instances, a population of substantially purified cells refers to a homogenous population of cells. In other instances, this term refers simply to cells that have been separated from the cells with which they are naturally associated in their natural state, or have been separated / isolated / purified from naturally-occurring biological material. In some embodiments, the cells are cultured in vitro. In other embodiments, the cells are not cultured in vitro.Cells described herein may comprise a combination of TCRs, e.g., one or more TCRs according to the present disclosure, and optionally one or more further TCRs. The TCRs may be introduced into the cells via the same nucleic acid / vector or via different nucleic acids / vectors.A plurality / population of cells described herein may comprise two or more TCRs, including TCR(s) from the present disclosure. For example, cells within the plurality / population of cells may each comprise two or more TCRs. As another example, different cells within the plurality / population of cells may each comprise at least one TCR, where the TCRs are identical or non-identical. Different TCRs may be individually transduced into different host cells.A number of TCR-Ts have been produced and are presently undergoing clinical trials. These TCR-Ts are described in Table 1 of Shafer et al., Front Immunol. (2022) 13:835762, which is hereby incorporated by reference in its entirety.A host cell / immune cell comprising an antigen-binding molecule, e.g., a TCR, or a nucleic acid encoding an antigen-binding molecule, e.g., a TCR, according to the present disclosure may be characterised by reference to functional properties of the cell. In some embodiments a host cell / immune cell comprising an antigen-binding molecule, e.g., a TCR, or a nucleic acid encoding an antigen-binding molecule, e.g., a TCR, according to the present disclosure displays one or more of the following properties:(a) expression of one or more cytotoxic / effector factors (e.g., IFNy, granzyme, perforin, granulysin, CD107a, TNFa, FASL) in response to cells presenting the MHC:peptide complex for which the TCR is specific;(b) proliferation / population expansion, and / or growth factor (e.g., IL-2, GM-CSF) expression in response to cells presenting the MHC:peptide complex for which the TCR is specific;(c) cytotoxicity to cells presenting the MHC:peptide complex for which the TCR is specific;(d) substantially no cytotoxicity or no cytotoxicity (i.e., same as or below baseline) to cells which do not present the MHC:peptide complex for which the TCR is specific; and(e) anti-cancer activity (e.g., cytotoxicity to cancer cells, tumor growth inhibition, reduction of metastasis, etc.) against cancer comprising cells presenting the MHC:peptide complex for which the TCR is specific.As used herein, ‘expression’ may be gene expression or protein expression. Gene expression encompasses transcription of DNA to RNA, and can be measured by various means known to those skilled in the art, for example by measuring levels of mRNA by quantitative real-time PCR (qRT-PCR), orby reporter-based methods. Similarly, protein expression can be measured by various methods well known in the art, e.g., by antibody-based methods, for example by western blot, immunohistochemistry, immunocytochemistry, flow cytometry, ELISA, ELISPOT, or reporter-based methods.Cell proliferation / population expansion can be investigated by analysing cell division or the number of cells over a period of time. Cell division can be analysed, for example, by in vitro analysis of incorporation of3H-thymidine or by CFSE dilution assay, e.g., as described in Fulcher and Wong, Immunol Cell Biol (1999) 77(6): 559-564, hereby incorporated by reference in its entirety. Proliferating cells can also be identified by analysis of incorporation of 5-ethynyl-2'-deoxyuridine (Edll) by an appropriate assay, as described e.g., in Buck et al., Biotechniques. 2008 Jun; 44(7):927-9, and Sali and Mitchison, PNAS USA 2008 Feb 19; 105(7): 2415-2420, both hereby incorporated by reference in their entirety.Cytotoxicity and cell killing can be investigated, for example, using any of the methods reviewed in Zaritskaya et al., Expert Rev Vaccines (201 1 ), 9(6):601 -616, hereby incorporated by reference in its entirety. Examples of in vitro assays of cytotoxicity / cell killing assays include release assays such as the51Cr release assay, the lactate dehydrogenase (LDH) release assay, the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) release assay, and the calcein-acetoxymethyl (calcein-AM) release assay. These assays measure cell killing based on the detection of factors released from lysed cells. Cell killing by a given cell type can be analysed e.g., by co-culturing the test cells with the given cell type, and measuring the number / proportion of viable / dead test cells after a suitable period of time. Other suitable assays include the xCELLigence real-time cytolytic in vitro potency assay described in Cerignoli et al., PLoS One. (2018) 13(3): e0193498 (hereby incorporated by reference in its entirety).Cells may be evaluated for anti-cancer activity by analysis in an appropriate in vitro assay or in vivo model of the relevant cancer.Methods for producing cells comprising / expressing an antigen-binding molecule / TCR of interest are well known to the skilled person, and generally comprise introducing nucleic acid(s) / vector(s) encoding constituent polypeptide(s) of the antigen-binding molecule / TCR into the cells.Such methods may comprise nucleic acid transfer for permanent ( .e., stable) or transient expression of the transferred nucleic acid. The transfer may involve methods of transfection, transformation or transduction. The term ‘transfected’ or ‘transformed’ or ‘transduced’ as used herein refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A ‘transfected’ or ‘transformed’ or ‘transduced’ cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. In some embodiments, following introduction into a cell, nucleic acid(s) encoding the polypeptide(s) of the TCR may be integrated into or form part of the genomic DNA of the cell. In some embodiments, following introduction into a cell, nucleic acid(s) encoding the polypeptide(s) may be maintained extrachromosomally.Any suitable genetic engineering platform may be used, and include gammaretroviral vectors, lentiviral vectors, adenovirus vectors, DNA transfection, transposon-based gene delivery and RNA transfection, forexample as described in Maus et al., Annu Rev Immunol (2014) 32:189-225, hereby incorporated by reference in its entirety. Methods also include those described e.g., in Wang and Riviere Mol Ther Oncolytics. (2016) 3:16015, which is hereby incorporated by reference in its entirety. Suitable methods for introducing nucleic acid(s) / vector(s) into cells include transduction, transfection and electroporation.Methods for generating / expanding populations of cells comprising / expressing the TCR in vitro / ex vivo are well known to the skilled person. Suitable culture conditions (i.e., cell culture media, additives, stimulations, temperature, gaseous atmosphere), cell numbers, culture periods and methods for introducing nucleic acid(s) / vector(s) encoding polypeptide(s) of interest into cells, etc. can be determined by reference e.g., to WO2018 / 177966 A1. In some embodiments, a cell / population of cells according to the present disclosure is prepared under GMP (good manufacturing practice; e.g., as described in the guidelines for good manufacturing practice published by the European Commission (Volume 4 of ‘The rules governing medicinal products in the European Union’ contains guidance for the interpretation of the principles and guidelines of good manufacturing practices for medicinal products for human and veterinary use laid down in Commission Directives 91 / 356 / EEC, as amended by Directive 2003 / 94 / EC, and 91 / 412 / EEC respectively)) conditions.Conveniently, cultures of cells according to the present disclosure may be maintained at 37°C in a humidified atmosphere containing 5% CO2. The cells of cell cultures can be established and / or maintained at any suitable density, as can readily be determined by the skilled person. Cultures can be performed in any vessel suitable for the volume of the culture, e.g., in wells of a cell culture plate, cell culture flasks, a bioreactor, etc. In some embodiments cells are cultured in a bioreactor, e.g., a bioreactor described in Somerville and Dudley, Oncoimmunology (2012) 1 (8): 1435-1437, which is hereby incorporated by reference in its entirety.Introducing nucleic acid(s) into a cell may comprise transduction, e.g., lentiviral transduction. Transduction of immune cells with viral vectors is described e.g., in Simmons and Alberola-lla, Methods Mol Biol. (2016) 1323:99-108, which is hereby incorporated by reference in its entirety.Introducing nucleic acid(s) into a cell comprise transfection, e.g., mRNA transfection. Transfection of immune cells with mRNA is described e.g., in Campillo-Davo et al., Pharmaceutics (2021 ) 13(3):396 and Chong et al., PeerJ (2021 ) 9:e11165 which are hereby incorporated by reference in their entirety.Agents may be employed to enhance the efficiency of transduction / transfection. Hexadimethrine bromide (polybrene) is a cationic polymer which is commonly used to improve transduction, through neutralising charge repulsion between virions and sialic acid residues expressed on the cell surface. Other agents commonly used to enhance transduction / transfection include e.g., the poloxamer-based agents such as LentiBOOST (Sirion Biotech), Retronectin (Takara), Vectofusin (Miltenyi Biotech) and also SureENTRY (Qiagen) and ViraDuctin (Cell Biolabs). In some embodiments the methods comprise centrifuging the cells into which it is desired to introduce nucleic acid encoding polypeptide(s) of the TCR in the presence of cell culture medium comprising viral vector comprising the nucleic acid (referred to in the art as ‘spinfection’).The methods generally comprise introducing a nucleic acid encoding polypeptide(s) of the TCR into a cell, and culturing the cell under conditions suitable for expression of the polypeptide(s) by the cell. In some embodiments, the methods comprise culturing immune cells into which nucleic acid encoding the polypeptide(s) has been introduced, in order to expand their number.In some embodiments, the methods comprise analysing the cells to confirm successful introduction of the nucleic acid into the cells. In some embodiments, the methods comprise analysing the cells to confirm expression of the polypeptide(s) by the cells (e.g., via evaluation of a detectable entity).In some embodiments the methods further comprise separating / isolating / purifying / enriching cells expressing the TCR e.g., from other cells (e.g., cells which do not express the TCR). Methods for purifying / isolating immune cells from heterogeneous populations of cells are well known in the art, and may employ e.g., FACS- or MACS-based methods for sorting populations of cells based on the expression of the TCR / constituent polypeptide(s) thereof. In some embodiments, the methods comprise separating / isolating / purifying / enriching cells of a particular type, e.g., CD8+ T cells or CTLs expressing the TCR of interest.Methods for producing cells according to the present disclosure may comprise modifying the cells to reduce the expression of a CD3-TCR complex polypeptide. In some embodiments, the methods comprise modifying nucleic acid (e.g., endogenous nucleic acid) encoding the CD3-TCR complex polypeptide. Modification of a given target nucleic acid can be achieved in a variety of ways known to the skilled person, including modification of the target nucleic acid by homologous recombination, and target nucleic acid editing using site-specific nucleases (SSNs).Suitable methods may employ targeting by homologous recombination, which is reviewed, for example, in Mortensen Curr Protoc Neurosci. (2007) Chapter 4:Unit 4.29 and Vasquez et al., PNAS 2001 , 98(15): 8403-8410 both of which are hereby incorporated by reference in their entirety. Targeting by homologous recombination involves the exchange of nucleotide sequence through crossover events guided by homologous sequences. Other suitable techniques include nucleic acid editing using SSNs. Gene editing using SSNs is reviewed e.g., in Eid and Mahfouz, Exp Mol Med. 2016 Oct; 48(10): e265, which is hereby incorporated by reference in its entirety. Enzymes capable of creating site-specific double strand breaks (DSBs) can be engineered to introduce DSBs to target nucleotide sequence(s) of interest. DSBs may be repaired by either error-prone non-homologous end-joining (NHEJ), in which the two ends of the break are rejoined, often with insertion or deletion of nucleotides. Alternatively, DSBs may be repaired by homology-directed repair (HDR), a high-fidelity mechanism in which a DNA template with ends homologous to the break site is supplied and introduced at the site of the DSB.SSNs capable of being engineered to generate target nucleotide sequence-specific DSBs include zinc- finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced palindromic repeats / CRISPR-associated-9 (CRISPR / Cas9) systems. ZFN systems are reviewed e.g., in Umov et al., Nat Rev Genet. (2010) 11 (9):636-46, which is hereby incorporated byreference in its entirety. ZFNs comprise a programmable Zinc Finger DNA-binding domain and a DNA- cleaving domain (e.g., a Fokl endonuclease domain). The DNA-binding domain may be identified by screening a Zinc Finger array capable of binding to the target nucleotide sequence. TALEN systems are reviewed e.g., in Mahfouz et al., Plant Biotechnol J. (2014) 12(8): 1006-14, which is hereby incorporated by reference in its entirety. TALENs comprise a programmable DNA-binding TALE domain and a DNA- cleaving domain (e.g., a Fokl endonuclease domain). TALEs comprise repeat domains consisting of repeats of 33-39 amino acids, which are identical except for two residues at positions 12 and 13 of each repeat which are repeat variable di-residues (RVDs). Each RVD determines binding of the repeat to a nucleotide in the target DNA sequence according to the following relationship: 'HD' binds to C, ‘NT binds to A, ‘NG’ binds to T and ‘NN’ or ‘NK’ binds to G (Moscou and Bogdanove, Science (2009) 326(5959):1501.). CRISPR / Cas9 and related systems e.g., CRISPR / Cpfl , CRISPR / C2c1 , CRISPR / C2c2 and CRISPR / C2c3 are reviewed e.g., in Nakade et al., Bioengineered (2017) 8(3):265-273, which is hereby incorporated by reference in its entirety. These systems comprise an endonuclease (e.g., Cas9, Cpf1 etc.) and the single-guide RNA (sgRNA) molecule. The sgRNA can be engineered to target endonuclease activity to nucleotide sequences of interest.In some embodiments, modifying nucleic acid (e.g., endogenous nucleic acid) encoding the CD3-TCR complex polypeptide in accordance with the present disclosure employs a site-specific nuclease (SSN) system targeting nucleic acid encoding the CD3-TCR complex polypeptide. The SSN system may be a ZFN system, a TALEN system, CRISPR / Cas9 system, a CRISPR / Cpf1 system, a CRISPR / C2c1 system, a CRISPR / C2c2 system or a CRISPR / C2c3 system.In some embodiments, a method for producing a cell according to the present disclosure comprises introducing nucleic acid(s) encoding CRISPR / Cas9 system(s) targeting TRAC, TRBC1 and / or TRBC2 (e.g., TRAC and TRBC1 ) into a cell. In some embodiments, the nucleic acid(s) encode a CRISPR RNA (crRNA) targeting TRAC, TRBC1 and / or TRBC2 (e.g., TRAC and TRBC1 ; e.g., an exon of TRAC, TRBC1 and / or TRBC2 (e.g., TRAC and TRBC1 )) and a trans-activating crRNA (tracrRNA) for processing the crRNA to its mature form.T Cell ReceptorsThe present disclosure provides antigen-binding molecules (e.g., T cell receptors) and fragments, chains, polypeptides and complexes thereof. The present disclosure provides a cell, or a plurality / population of cells, comprising / expressing antigen-binding molecules (e.g., T cell receptors) and fragments, chains, polypeptides and complexes thereof, according to the present disclosure.The term ‘T cell receptor’ (TCR), as used herein, refers to a heteromeric cell-surface receptor capable of specifically interacting with a target antigen. Herein, a ‘TCR’ or an antigen-binding fragment thereof may also be referred to as an ‘antigen-binding molecule’. As used herein, ‘TCR’ includes but is not limited to: naturally occurring and non-naturally occurring TCRs; full-length TCRs and antigen-binding portions thereof, chimeric TCRs; TCR fusion constructs; and synthetic TCRs. In humans, TCRs are expressed on the surface of T cells, and they are responsible for T cell recognition and targeting of antigen presenting cells. Antigen presenting cells (APC) display fragments of foreign or self-proteins (antigens) complexedwith the major histocompatibility complex (MHC; also referred to herein as complexed with a HLA molecule, e.g., a HLA class I or class II molecule). A TCR recognizes and binds to the antigemHLA complex and recruits CD3 (expressed by T cells), activating the TCR. The activated TCR initiates downstream signaling and an immune response, including the destruction of the APC.In general, a TCR can comprise two chains, an alpha chain and a beta chain (or less commonly a gamma chain and a delta chain), interconnected by disulfide bonds to form a heterodimeric receptor. Each chain comprises a variable domain (e.g., alpha chain variable domain or beta chain variable domain) and a constant region (e.g., alpha chain constant region or beta chain constant region). The variable domain is located distal to the cell membrane, and interacts with an antigen. A variable domain may also be referred to herein as a ‘variable region’. The constant region is located proximal to the cell membrane, acts to anchor the protein in the cell membrane, and associates with invariant subunits of the CD3 signaling apparatus. A TCR can further comprise a transmembrane region and a short cytoplasmic tail. As used herein, the term ‘constant region’ encompasses the transmembrane region and the cytoplasmic tail, when present, as well as the traditional ‘constant region.’The variable domains can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each alpha chain variable domain and beta chain variable domain comprises three CDRs and four FRs: FR1 , CDR1 , FR2, CDR2, FR3, CDR3, FR4.Each variable domain contains a binding domain that interacts with an antigen. This may be called an antigen-binding domain or antigen-binding fragment of a TCR. Together, the 6 CDRs form the majority of the antigen binding site of the TCR, thus conferring onto each TCR its specificity (Schroeder and Cavacini, J Allergy Clin Immunol 125(202):S41-S52 (2010); Bhati et al., Protein Science 23:260-272 (2014), which are hereby incorporated by reference in their entirety). The CDRs interact with a complex between an antigenic peptide bound to a protein encoded by the major histocompatibility complex (pepMHC) (Davis and Bjorkman (1988) Nature, 334, 395-402; Davis et al. (1998) Annu Rev Immunol, 16, 523-544; Murphy (2012), xix, 868 p., which are hereby incorporated by reference in their entirety). Although all three CDRs on each chain are involved in antigen binding, CDR3 is believed to be the primary antigen binding region, interacting with the peptide in the HLA complex groove during TCR binding. CDR1 and CDR2 are believed to primarily recognize the HLA complex.The term CDR3 used herein describes the CDR3 region optionally including the fixed C’-terminal amino acid C (cysteine) and N'-terminal amino acid F (phenylalanine) or W (Tryptophan), or the respective nucleotide sequences coding for these amino acids. The CDR3 including C’-terminal C and N’-terminal F / W, or the respective codons, is also termed ‘Junction’ in the field.An antigen-binding molecule, e.g., TCR, may be capable of binding to an antigen, e.g., an antigen according to the present disclosure. An antigen-binding molecule, e.g., TCR, may bind to an antigen, e.g., an antigen according to the present disclosure.An antigen-binding molecule, e.g., a TCR or fragment / chain thereof, may bind to an antigen-derived peptide, such as when presented by a major histocompatibility complex (MHC) molecule.In some embodiments, the antigen-binding molecule comprises the CDRs of a TCR that binds to an antigen-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). In some embodiments, the antigen-binding molecule comprises the FRs of a TCR that binds to an antigen-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). In some embodiments, the antigen-binding molecule comprises the CDRs and the FRs of a TCR that binds to an antigen-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). That is, in some embodiments, the antigen-binding molecule comprises the TCRa variable domain and the TCR0 variable domain of a TCR that binds to an antigen-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). The antigen- derived peptide may be an antigen-derived peptide according to the present disclosure.The present invention provides an antigen-binding molecule, e.g., a TCR or fragment / chain thereof, that binds to a WT-1 -derived, MAGE-A1 -derived, MAGE-A10-derived, MAGE-A4-derived or PRAME-derived antigenic peptide, such as when presented by a major histocompatibility complex (MHC) molecule.In some embodiments, the antigen-binding molecule comprises the CDRs of a TCR that binds to a WT-1- derived, MAGE-A1 -derived, MAGE-A10-dervied, MAGE-A4-derived or PRAME-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). In some embodiments, the antigen-binding molecule comprises the FRs of a TCR that binds to WT-1-derived, MAGE-A1 -derived, MAGE-A10-dervied, MAGE-A4-derived or PRAME-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). In some embodiments, the antigen-binding molecule comprises the CDRs and the FRs of a TCR that binds to a WT-1 -derived, MAGE-A1 -derived, MAGE-A10- dervied, MAGE-A4-derived or PRAME-derived peptide (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). That is, in some embodiments, the antigen-binding molecule comprises the TCRa variable domain and the TCRfJ variable domain of a TCR that binds to a WT-1- derived, MAGE-A1 -derived, MAGE-A10-dervied, MAGE-A4-derived or PRAME-derived (e.g., such as when presented by a major histocompatibility complex (MHC) molecule). The WT-1-derived, MAGE-A1- derived, MAGE-A10-dervied, MAGE-A4-derived or PRAME-derived peptide may be any such peptide according to the present disclosure. The WT-1 -derived peptide may be SEQ ID NO:1 , 179, 180, 181 or 182. The WT-1-derived peptide may be SEQ ID NO:1 , 179, 180, 181 or 182 and may be presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01. The MAGE-A1 -derived peptide may be SEQ ID NO: 191 or 223 and may be presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01. The MAGE-A10-derived peptide may be SEQ ID NO:225 or 226 and may be presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01. The MAGE-A10-derived peptide may be SEQ ID NO:227 or 228 and may be presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*24, e.g., encoded by HLA-A*24:02.An antigen-binding molecule, e.g., TCRs, TCR polypeptides, and fragments / chains thereof, may comprise one or more of: the TCRa and TCR0 CDR sequences listed in Table A, the FR sequences listed in Table B, the TCRa and TCR0 variable domain amino acid sequences listed in Table C, and / or the TCRa and TCR0 variable domains encoded by the nucleotide sequences listed in Table D.Where not expressly stated, and unless the context indicates otherwise, the term ‘TCR’ also includes an antigen-binding fragment or an antigen-binding portion of any TCR disclosed herein, and includes a monovalent and a divalent fragment or portion, and a single chain TCR or TCR fragment. An ‘antigenbinding molecule,’ ‘portion of a TCR,’ or ‘TCR fragment’ may refer to a portion of a TCR less than the whole. An ‘antigen-binding molecule’, ‘portion of a TCR,’ or ‘TCR fragment’ can include the antigenic complementarity determining regions (CDRs).The term ‘TCR’ is not limited to naturally occurring TCRs bound to the surface of a T cell. As used herein, the term ‘TCR’ further refers to a TCR described herein that is expressed on the surface of a cell other than a T cell (e.g., a cell that naturally expresses or that is modified to express CD3, as described herein), or a TCR described herein that is free from a cell membrane (e.g., an isolated TCR or a soluble TCR). Thus, in some embodiments, an antigen-binding molecule, e.g., TCR or TCR chain / polypeptide, described herein is provided in isolated or purified form. For example, articles according to the present disclosure may be isolated / purified from naturally-occurring biological material. In some embodiments, an antigen-binding molecule described herein, e.g., TCR or TCR chain / polypeptide, is soluble. In some embodiments, an antigen-binding molecule described herein, e.g., TCR or TCR chain / polypeptide, (or a nucleotide sequence encoding the antigen-binding molecule) is comprised within and / or expressed by a cell, e.g., a cell as described herein. In some embodiments, the TCR chain sequences are listed together with the leader sequence preceding FR1. The leader sequence regulates gene expression of the protein but is not present in the mature TCR protein. Example leader sequences for TCRa and TCR0 chains are provided in SEQ ID NO:170.In some embodiments, the antigen-binding molecule comprises the CDRs, FRs, and / or the alpha and / or beta chain variable domains of a TCR as described herein, or CDRs, FRs, and / or the alpha and / or beta chain variable domains which are derived from those of a TCR described herein. In some embodiments, a TCR is selected from TCR_A0431 , TCR_A0427, TCR_A0426, TCR_A0428, TCR_A0429, TCR_A0430, TCR A0432, TCR_A0464, TCR_A0360, TCR_A0387, TCR_A0385, TCR_A0390, TCR_A0398, TCR A0409, TCR A0425, TCR A0435, TCR A0436. In some embodiments, a TCR is selected from TCR A0431 and TCR A0427. In some embodiments, a TCR is TCR A0387.In some embodiments, an antigen-binding molecule is selected from TCR_A0431 , TCR_A0427, TCR A0426, TCR_A0428, TCR_A0429, TCR_A0430, TCR_A0432, TCR_A0464, TCR_A0360, TCR A0387, TCR_A0385, TCR_A0390, TCR_A0398, TCR_A0409, TCR_A0425, TCR_A0435, TCR_A0436. In some embodiments, an antigen-binding molecule is selected from TCR_A0431 and TCR_A0427. In some embodiments, an antigen-binding molecule is TCR_A0387.In some embodiments the antigen-binding molecule comprises a TCRa chain, or a fragment thereof. In some embodiments, the TCRa chain comprises a TCRa variable domain.In some embodiments, the TCRa variable domain, comprises a CDR3a having an amino acid sequence of SEQ ID NO:34, 10, 4, 16, 22, 28, 40, 46, 194, 231 , 237, 243, 249, 255, 261 or 267 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:34, 10, 4, 16, 22, 28, 40, 46, 194, 231 , 237, 243, 249, 255, 261 or 267 are substituted with another amino acid).In some embodiments the antigen-binding molecule comprises a TCR0 chain, or a fragment thereof. In some embodiments, the TCR chain comprises a TCR variable domain.In some embodiments, the TCRfJ variable domain, comprises a CDR3 having an amino acid sequence of SEQ ID NO:37, 13, 7, 19, 25, 31 , 43, 49, 197, 234, 240, 246, 252, 258, 264 or 270 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:37, 13, 7, 19, 25, 31 , 43, 49, 197, 234, 240, 246, 252, 258, 264 or 270 are substituted with another amino acid).In some embodiments, the antigen-binding molecule comprises: (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:34, 10, 4, 16, 22, 28, 40, 46, 194, 231 , 237, 243, 249, 255, 261 or 267 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:34, 10, 4, 16, 22, 28, 40, 46, 194, 231 , 237, 243, 249, 255, 261 or 267 are substituted with another amino acid); in combination with (ii) a TCR|3 variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:37, 13, 7, 19, 25, 31 , 43, 49, 197, 234, 240, 246, 252, 258, 264 or 270 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:37, 13, 7, 19, 25, 31 , 43, 49, 197, 234, 240, 246, 252, 258, 264 or 270 are substituted with another amino acid).In some embodiments, the antigen-binding molecule comprises: (i) a TCRa variable domain comprising a CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A; in combination with (ii) a TCR variable domain comprising a CDR3 (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A; wherein the CDR3a amino acid sequence from Column A and the CDR30 amino acid sequence from Column B are selected from the same row.By way of illustration, in some embodiments, the antigen-binding molecule comprises: (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:34 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 34 are substituted with another amino acid) (row 6); in combination with (ii) a TCR|3 variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:37 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:37 are substituted with another amino acid) (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises: (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO: 10 (or a variantthereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 10 are substituted with another amino acid) (row 2); in combination with (ii) a TCRp variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO: 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 13 are substituted with another amino acid) (row 2).In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of Table A.In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A are selected from the same row of Table A.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising:CDR1a having an amino acid sequence of SEQ ID NO:32 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:32 are substituted with another amino acid) (row 6);CDR2a having an amino acid sequence of SEQ ID NO:33 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:33 are substituted with another amino acid) (row 6); and / orCDR3a having an amino acid sequence of SEQ ID NO:34 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:34 are substituted with another amino acid) (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising:CDR1a having an amino acid sequence of SEQ ID NO:8 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:8 are substituted with another amino acid) (row 2);CDR2a having an amino acid sequence of SEQ ID NO:9 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:9 are substituted with another amino acid) (row 2); and / orCDR3a having an amino acid sequence of SEQ ID NO: 10 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 10 are substituted with another amino acid) (row 2).In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid)and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of Table B.In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and / or FR4 sequences of Column A are selected from the same row of Table B.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 138, 139,140 and 141 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 138, 139, 140 and / or141 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 106, 107, 108 and 109 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 106, 107, 108 and / or 109 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A are selected from the same row of Table A; and FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and / or FR4 sequences of Column A are selected from the same row of Table B.In some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A areselected from the same row of Table A; and FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and / or FR4 sequences of Column A are selected from the same row of Table B; wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A of Table A and the FR1 , FR2, FR3 and / or FR4 of Column A of Table B are selected from rows having the same number.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising: CDR1a, CDR2a and / or CDR3a having an amino acid sequence of SEQ ID NO:32, 33 and 34 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:32, 33 and / or 34 are substituted with another amino acid), respectively (row 6); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 138, 139, 140 and 141 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 138, 139, 140 and / or 141 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCRa variable domain comprising: CDR1a, CDR2a and / or CDR3a having an amino acid sequence of SEQ ID NO:8, 9 and 10 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:8, 9 and / or 10 are substituted with another amino acid), respectively (row 2); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 106, 107, 108 and 109 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NQ:106, 107, 108 and / or 109 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises a TCRa variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, 80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NQ:60, 52, 50, 54, 56, 58, 62, 64, 198, 271 , 273, 275, 277, 279, 281 or 283.In some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising CDRip (or a variant thereof in which 1 or 2 or 3 amino acids in CDRip are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2 are substituted with another amino acid) and / or CDR3 (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of Table A.In some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising CDRip (or a variant thereof in which 1 or 2 or 3 amino acids in CDRip are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12,13, 14, 15 or 16 of Table A, wherein the CDR10, CDR20 and / or CDR30 sequences of Column B are selected from the same row of Table A.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising:CDR10 having an amino acid sequence of SEQ ID NO:35 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:35 are substituted with another amino acid) (row 6);CDR20 having an amino acid sequence of SEQ ID NO:36 (or a variant thereof in which 1 or 2 or3 amino acids in SEQ ID NO:36 are substituted with another amino acid) (row 6); and / orCDR30 having an amino acid sequence of SEQ ID NO:37 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:37 are substituted with another amino acid) (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising:CDR10 having an amino acid sequence of SEQ ID NO:1 1 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:1 1 are substituted with another amino acid) (row 2);CDR20 having an amino acid sequence of SEQ ID NO: 12 (or a variant thereof in which 1 or 2 or3 amino acids in SEQ ID NO: 12 are substituted with another amino acid) (row 2); and / orCDR30 having an amino acid sequence of SEQ ID NO: 13 (or a variant thereof in which 1 or 2 or3 amino acids in SEQ ID NO: 13 are substituted with another amino acid) (row 2).In some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of Table B.In some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and FR4 sequences of Column B are selected from the same row of Table B.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCR0 variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:142, 143, 144, and 145 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 142, 143, 144, and / or 145 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:1 10, 1 1 1 , 1 12 and 1 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:1 10, 1 1 1 , 1 12 and / or 1 13 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising: CDRi p (or a variant thereof in which 1 or 2 or 3 amino acids in CDRi p are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or 16 of Table A, wherein CDRi p, CDR2P and / or CDR3P sequences of Column B are selected from the same row of Table A; and FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or 16 of Table B, wherein FR1 , FR2, FR3 and / or FR4 sequences of Column B are selected from the same row of Table B.In some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising: CDRi p (or a variant thereof in which 1 or 2 or 3 amino acids in CDRi p are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or 16 of Table A, wherein CDRi p, CDR2P and / or CDR3P sequences of Column B are selected from the same row of Table A; and FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or 16 of Table B, wherein FR1 , FR2, FR3 and / or FR4 sequences of Column B are selected from the same row of Table B; wherein the CDR1 p, CDR2P and / or CDR3P sequences of Column B of Table A and the FR1 , FR2, FR3 and / or FR4 of Column B of Table B are selected from rows having the same number.By way of illustration, in some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising: CDR1 p, CDR2P and / or CDR3P having an amino acid sequence of SEQ ID NO:35, 36 and 37 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:35, 36 and / or 37 are substituted with another amino acid), respectively (row 6); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 142, 143, 144 and 145 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:142, 143, 144 and / or 145 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises a TCRp variable domain comprising: CDR1 p, CDR2p and / or CDR3 having an amino acid sequence of SEQ ID NO:11 , 12 and 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:11 , 12 and / or 13 are substituted with another amino acid), respectively (row 2); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:110, 111 , 112 and 113 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:110, 111 , 112 and / or 113 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises a TCR variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, 80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:61 , 53, 51 , 55, 57, 59, 63, 65, 199, 272, 274, 276, 278, 280, 282 or 284.In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of Table A; in combination with,(ii) a TCR variable domain comprising: a TCRp variable domain comprising CDR1P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1 p are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of Table A.In some embodiments, the antigen-binding molecule comprises:(I) a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1 a, CDR2a and / or CDR3a sequences of Column A are selected from the same row of Table A; in combination with(II) a TCRp variable domain comprising CDR1P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1 p are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1 p, CDR2p and / or CDR3P sequences of Column B are selected from the same row of Table A.In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1 a, CDR2a and / or CDR3a sequences of Column A are selected from the same row of Table A; in combination with(ii) a TCRp variable domain comprising CDR1P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1 p are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A, wherein the CDR1 p, CDR2P and / or CDR3P sequences of Column B are selected from the same row of Table A; wherein the CDR1a, CDR2a and / or CDR3a amino acid sequences from Column A and the CDRip, CDR2P and / or CDR3P amino acid sequences from Column B are selected from the same row.By way of illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: CDR1a having an amino acid sequence of SEQ ID NO:32 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:32 are substituted with another amino acid) (row 6); CDR2a having an amino acid sequence of SEQ ID NO:33 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:33 are substituted with another amino acid) (row 6); and / or CDR3a having an amino acid sequence of SEQ ID NO:34 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:34 are substituted with another amino acid) (row 6); in combination with(ii) a TCRP variable domain comprising: CDR1 p having an amino acid sequence of SEQ ID NO:35 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:35 are substituted with another amino acid) (row 6); CDR2P having an amino acid sequence of SEQ ID NO:36 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:36 are substituted with another amino acid) (row 6); and / or CDR3P having an amino acid sequence of SEQ ID NO:37 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:37 are substituted with another amino acid) (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: CDR1a having an amino acid sequence of SEQ ID NO:8 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:8 are substituted with another amino acid) (row 2); CDR2a having an amino acid sequence of SEQ ID NO:9 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:9 are substituted with another amino acid) (row 2); and / or CDR3a having an amino acid sequence of SEQ ID NO:10 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 10 are substituted with another amino acid) (row 2); in combination with(ii) a TCRp variable domain comprising: CDR1 p having an amino acid sequence of SEQ ID NO:11 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:11 are substituted with another amino acid) (row 2); CDR2P having an amino acid sequence of SEQ ID NO: 12 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 12 are substituted with another amino acid) (row 2); and / or CDR3P having an amino acid sequence of SEQ ID NO: 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:13 are substituted with another amino acid) (row 2).In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of Table B; in combination with,(ii) a TCRP variable domain comprising: FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of Table B.In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and / or FR4 sequences of Column A are selected from the same row of Table B; in combination with(ii) a TCRp variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and FR4 sequences of Column B are selected from the same row of Table B.In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and / or FR4 sequences of Column A are selected from the same row of Table B; in combination with,(ii) a TCRp variable domain comprising FR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B, wherein the FR1 , FR2, FR3 and FR4 sequences of Column B are selected from the same row of Table B; wherein the FR1 , FR2, FR3 and / or FR4 amino acid sequences from Column A and the FR1 , FR2, FR3 and / or FR4 amino acid sequences from Column B are selected from the same row.By way of illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising FR1, FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 138, 139, 140 and 141 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 138, 139, 140 and / or 141 are substituted with another amino acid), respectively (row 6); in combination with,(ii) a TCRfJ variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 142, 143, 144, and 145 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 142, 143, 144, and / or 145 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 106, 107, 108 and 109 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 106, 107, 108 and / or 109 are substituted with another amino acid), respectively (row 2); in combination with,(ii) a TCRfJ variable domain comprising FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:110, 111 , 112 and 113 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:110, 111 , 112 and / or 113 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises:(I) a TCRa variable domain comprising:CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A; andFR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B; wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A of Table A, and the FR1 , FR2, FR3 and / or FR4 of Column A of Table B are selected from rows having the same number; in combination with(ii) a TCRp variable domain comprising:CDRip (or a variant thereof in which 1 or 2 or 3 amino acids in CDRip are substituted with another amino acid), CDR2 (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2p are substituted with another amino acid) and / or CDR3p (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table A; andFR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B; wherein the CDR1 p, CDR2P and / or CDR3P sequences of Column B of Table A, and the FR1 , FR2, FR3 and / or FR4 of Column B of Table B are selected from rows having the same number.In some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising:CDR1a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR1a are substituted with another amino acid), CDR2a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2a are substituted with another amino acid) and / or CDR3a (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3a are substituted with another amino acid), as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8,9, 10, 11 , 12, 13, 14, 15 or 16 of Table A; andFR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B; in combination with(ii) a TCRp variable domain comprising:CDRip (or a variant thereof in which 1 or 2 or 3 amino acids in CDRip are substituted with another amino acid), CDR2P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR2P are substituted with another amino acid) and / or CDR3P (or a variant thereof in which 1 or 2 or 3 amino acids in CDR3P are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9,10, 11 , 12, 13, 14, 15 or 16 of Table A; andFR1 (or a variant thereof in which 1 or 2 or 3 amino acids in FR1 are substituted with another amino acid), FR2 (or a variant thereof in which 1 or 2 or 3 amino acids in FR2 are substituted with another amino acid), FR3 (or a variant thereof in which 1 or 2 or 3 amino acids in FR3 are substituted with another amino acid) and / or FR4 (or a variant thereof in which 1 or 2 or 3 amino acids in FR4 are substituted with another amino acid) as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table B; wherein the CDR1a, CDR2a and / or CDR3a sequences of Column A of Table A; the FR1, FR2, FR3 and / or FR4 of Column A of Table B; the CDR1 p, CDR2P and / or CDR3P sequences of ColumnB of Table A; and the FR1 , FR2, FR3 and / or FR4 of Column B of Table B are selected from rows having the same number.By way of illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: CDR1a, CDR2a and / or CDR3a having an amino acid sequence of SEQ ID NO:32, 33 and 34 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:32, 33 and / or 34 are substituted with another amino acid), respectively (row 6); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO: 138, 139, 140 and 141 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 138, 139, 140 and / or 141 are substituted with another amino acid), respectively (row 6); in combination with,(ii) a TCR0 variable domain comprising: CDR1 , CDR20 and / or CDR30 having an amino acid sequence of SEQ ID NO:35, 36 and 37 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:35, 36 and / or 37 are substituted with another amino acid), respectively (row 6); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:142, 143, 144 and 145 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 142, 143, 144 and / or 145 are substituted with another amino acid), respectively (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises:(i) a TCRa variable domain comprising: CDR1a, CDR2a and / or CDR3a having an amino acid sequence of SEQ ID NO:8, 9 and 10 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:8, 9 and / or 10 are substituted with another amino acid), respectively (row 2); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NQ:106, 107, 108 and 109 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 106, 107, 108 and / or 109 are substituted with another amino acid), respectively (row 2); in combination with,(ii) a TCR0 variable domain comprising: CDR10, CDR20 and / or CDR30 having an amino acid sequence of SEQ ID NO:1 1 , 12 and 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO:1 1 , 12 and / or 13 are substituted with another amino acid), respectively (row 2); and FR1 , FR2, FR3 and / or FR4 having an amino acid sequence of SEQ ID NO:1 10, 1 1 1 , 1 12 and 1 13 (or a variant thereof in which 1 or 2 or 3 amino acids in SEQ ID NO: 1 10, 1 11 , 1 12 and / or 1 13 are substituted with another amino acid), respectively (row 2).In some embodiments, the antigen-binding molecule comprises: (i) a TCRa variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NQ:60, 52, 50, 54, 56, 58, 62, 64, 198, 271 , 273, 275, 277, 279, 281 or 283; in combination with (ii) a TCR0 variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of >75%, S80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:61 , 53, 51 , 55, 57, 59, 63, 65, 199, 272, 274, 276, 278, 280, 282 or 284.In some embodiments, the antigen-binding molecule comprises: (I) a TCRa variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity, with the TCRa variable domain amino acid sequence as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table C; in combination with (ii) a TCR[3 variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of >75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the TCR variable domain amino acid sequence as indicated in Column B row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 or 16 of Table C; wherein the TCRa variable domain amino acid sequence from Column A and the TCR0 variable domain amino acid sequence from Column B are selected from the same row.By way of illustration, in some embodiments, the antigen-binding molecule comprises: (I) a TCRa variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:60 (row 6); in combination with (ii) a TCRp variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:61 (row 6).By way of further illustration, in some embodiments, the antigen-binding molecule comprises: (I) a TCRa variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:52 (row 2); in combination with (ii) a TCR variable domain having an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:53 (row 2).In any of the embodiments disclosed herein, an antigen-binding molecule / TCR or fragment thereof comprising an amino acid sequence described by reference to a given SEQ ID NO or variant thereof in which 1 or 2 or 3 amino acids are substituted with another amino acid, may instead comprise an amino acid sequence having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of the given SEQ ID NO.In some embodiments described herein, one or more amino acids of an amino acid sequence referred to herein (e.g., an amino acid sequence of an antigen-binding molecule, e.g., an amino acid sequence of a CDR or variable domain) are substituted with another amino acid. A substitution comprises substitution of an amino acid residue with a non-identical ‘replacement’ amino acid residue. A replacement amino acid residue of a substitution according to the present disclosure may be a naturally-occurring amino acidresidue (i.e., encoded by the genetic code) which is non-identical to the amino acid residue at the relevant position of the equivalent, unsubstituted amino acid sequence, selected from: alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (lie): leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Vai). In some embodiments, a replacement amino acid may be a non-naturally occurring amino acid residue - i.e., an amino acid residue other than those recited in the preceding sentence. Examples of non-naturally occurring amino acid residues include norleucine, ornithine, norvaline, homoserine, alb, and other amino acid residue analogues such as those described in Ellman, et al., Meth. Enzym. 202 (1991 ) 301-336.In some embodiments, a substitution may be biochemically conservative. In some embodiments, where an amino acid to be substituted is provided in one of rows 1 to 5 of the table below, the replacement amino acid of the substitution is another, non-identical amino acid provided in the same row:By way of illustration, in some embodiments wherein substitution is of a Met residue, the replacement amino acid may be selected from Ala, Vai, Leu, lie, Trp, Tyr, Phe and Norleucine.In some embodiments, a replacement amino acid in a substitution may have the same side chain polarity as the amino acid residue it replaces. In some embodiments, a replacement amino acid in a substitution may have the same side chain charge (at pH 7.4) as the amino acid residue it replaces:That is, in some embodiments, a nonpolar amino acid is substituted with another, non-identical nonpolar amino acid. In some embodiments, a polar amino acid is substituted with another, non-identical polar amino acid. In some embodiments, an acidic polar amino acid is substituted with another, non-identical acidic polar amino acid. In some embodiments, a basic polar amino acid is substituted with another, non- identical basic polar amino acid. In some embodiments, a neutral amino acid is substituted with another, non-identical neutral amino acid. In some embodiments, a positive amino acid is substituted with another, non-identical positive amino acid. In some embodiments, a negative amino acid is substituted with another, non-identical negative amino acid.In some embodiments, substitution(s) may be functionally conservative. That is, in some embodiments, the substitution may not affect (or may not substantially affect) one or more functional properties (e.g., target binding) of the antigen-binding molecule comprising the substitution as compared to the equivalent unsubstituted molecule.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein, may be capable of binding to an antigen (e.g., an antigen described herein). In some embodiments, an antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 or PRAME. In some embodiments, an antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from WT-1 , MAGE-A1 or MAGE-A10.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from WT-1 , i.e., a WT-1 -derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, WT-1 comprises or consists of the amino acid sequence of SEQ ID NO:169. In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from WT-1 protein, i.e., a WT-1-derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, WT-1 comprises or consists of the amino acid sequence of SEQ ID NO:169, 184, 185,186, 187, 188, 189 or 190. In some embodiments, WT-1 comprises or consists of the amino acid sequence of SEQ ID NO:169, 184, 185, 186, 188, or 189.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from MAGE-A1 protein, i.e., a MAGE-A1- derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, MAGE-A1 comprises or consists of the amino acid sequence of SEQ ID NO:212.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from MAGE-A10 protein, i.e., a MAGE-A10- derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, MAGE-A10 comprises or consists of the amino acid sequence of SEQ ID NO:369.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from MAGE-A4 protein, i.e., a MAGE-A4- derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, MAGE-A4 comprises or consists of the amino acid sequence of SEQ ID NO:371.In some embodiments, any antigen-binding molecule, e.g., TCR or fragment thereof, described herein may be capable of binding to a peptide or antigen derived from PRAME, i.e., a PRAME-derived peptide or antigen, such as when presented by a major histocompatibility complex (MHC) molecule. In some embodiments, PRAME comprises or consists of the amino acid sequence of SEQ ID NO:372.For conciseness, hereinbelow a peptide that is presented by an MHC class I molecule comprising an MHC class I a chain polypeptide encoded by a given HLA allele or a HLA allele within a given genus of HLA alleles may be referred to simply as being presented ‘through’ or ‘on’ the relevant allele. For example, a TCR that binds to a WT-1 -derived antigenic peptide presented by an MHC class I molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele may be described as a TCR that binds to a WT-1 -derived antigenic peptide presented through / on a HLA-A*02 allele.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a WT-1 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by HLA-A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a WT-1 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, the antigen-binding molecule is capable of binding to a WT-1 -derived antigenic peptide presented through another HLA-A*02 allele, including but not restricted to: HLA-A*02:02, HLA- A*02:03, HLA-A*02:04, HLA-A*02:05, HLA-A*02:06, HLA-A*02:07, HLA-A*02:11 , HLA-A*02:12, HLA- A*02:19, HLA-A*02:24, HLA-A*02:264, or HLA-A*02:52.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:1 , 179, 180, 181 or 182, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by HLA-A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO: 1 , 179, 180, 181 or 182, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFAPPGA (SEQ ID NQ:1 )-HLA-A*02 complex. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFAPPGA (SEQ ID NO:1 )-HLA-A*02:01 complex.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFX1PPX2X3 (SEQ ID NQ:179)-HLA-A*02 complex. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFX1PPX2X3 (SEQ ID NQ:179)-HLA-A*02:01 complex. In some embodiments, the antigen-binding molecule capable of binding to a VLDFX1PPX2X3 (SEQ ID NQ:179)-HLA-A*02 complex or a VLDFX1PPX2X3 (SEQ ID NQ:179)-HLA-A*02:01 complex is TCR_A0427.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFX1X2PX3X4 (SEQ ID NQ:180)-HLA-A*02 complex. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFX1X2PX3X4 (SEQ ID NQ:180)-HLA-A*02:01 complex. In some embodiments, the antigen-binding molecule capable of binding to a VLDFX1X2PX3X4 (SEQ ID NQ:180)-HLA-A*02 complex or a VLDFX1X2PX3X4 (SEQ ID NQ:180)-HLA-A*02:01 complex is TCR_A0429.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VX1DFX2X3PX4X5 (SEQ ID NO:181 )-HLA-A*02 complex. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VX1DFX2X3PX4X5 (SEQ ID NQ:181 )-HLA-A*02:01 complex. In some embodiments, the antigen-binding molecule capable of binding to a VX1DFX2X3PX4X5 (SEQ ID NO: 181 )-HLA-A*02 complex or a VXIDFX2X3PX4X5(SEQ ID NO:181 )-HLA-A*02:01 complex is TCR_A0431.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFXIPX2GX3 (SEQ ID NQ:182)-HLA-A*02 complex. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a VLDFX1PX2GX3 (SEQ ID NQ:182)-HLA-A*02:01 complex. In some embodiments, the antigen-bindingmolecule capable of binding to a VLDFX1PX2GX3 (SEQ ID NO:182)-HLA-A*02 complex or a VLDFX1PX2GX3 (SEQ ID NO:182)-HLA-A*02:01 complex is TCR_A0432.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHO class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of SEQ ID NO:1 , 179, 180, 181 or 182.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VLDFAPPGA (SEQ ID NO:1).In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VLDFX1PPX2X3 (SEQ ID NO: 179). In some embodiments, the peptide comprises or consists of SEQ ID NO: 179, wherein Xi is A or any amino acid other than A, X2 is G or any amino acid other than G, and / or X3 is A or any amino acid other than A.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VLDFX1X2PX3X4 (SEQ ID NO: 180). In some embodiments, the peptide comprises or consists of SEQ ID NO: 180, wherein Xi is A or any amino acid other than A, X2 is P or any amino acid other than P, X3 is G or any amino acid other than G, and / or X4 is A or any amino acid other than A.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VX1DFX2X3PX4X5 (SEQ ID NO: 181 ). In some embodiments, the peptide comprises or consists of SEQ ID NO: 181 , wherein Xi is L or any amino acid other than L, X2 is A or any amino acid other than A, X3 is P or any amino acid other than P, X4 is G or any amino acid other than G, and / or X5 is A or any amino acid other than A.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VLDFX1PX2GX3 (SEQ ID NO: 182). In some embodiments, the peptide comprises or consists of SEQ ID NO: 182, wherein Xi is A or any amino acid other than A, X2 is P or any amino acid other than P, and / or X3 is A or any amino acid other than A.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A1 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by HLA-A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A1 peptide, e.g., when presented by a major histocompatibility complex (MHO) molecule comprising an MHO class I a chain polypeptide encoded by a HLA-A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, the antigen-binding molecule is capable of binding to a MAGE-A1 -derived antigenic peptide presented through another HLA-A*02 allele, including but not restricted to: HLA- A*02:02, HLA-A*02:03, HLA-A*02:04, HLA-A*02:05, HLA-A*02:06, HLA-A*02:07, HLA-A*02:11 , HLA- A*02:12, HLA-A*02:19, HLA-A*02:24, HLA-A*02:264, or HLA-A*02:52.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:191 or 223, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by HLA-A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:191 or 223, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a KVLEYVIKV (SEQ ID NO:191 )-HLA-A*02 complex.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a KVLEYVIKV (SEQ ID NQ:191 )-HLA-A*02:01 complex.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a KXIX2EX3VIX4X5(SEQ ID NQ:223)-HLA-A*02 complex.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a KX1X2EX3VIX4X5 (SEQ ID NQ:223)-HLA-A*02:01 complex.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of KVLEYVIKV (SEQ ID NO:191).In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of KX1X2EX3VIX4X5 (SEQ ID NO:223).In some embodiments, in SEQ ID NO: 223, Xi is V or any amino acid other than V, X2 is L or any amino acid other than L, X3 is Y or any amino acid other than Y, X4is K or any amino acid other than K, and / or X5 is V or any amino acid other than V.In some embodiments, in SEQ ID NO: 223, X3 is not Y and / or X4is not K.In some embodiments, in SEQ ID NO: 223, Xi is not V, X2 is not L, and / or X5 is not V.MAGE-A1 peptide KVLEYVIKV (SEQ ID NO: 191 ) has been reported as an immunogenic epitope presented on HLA-A*02:01 and TCRs against this peptide have been discovered previously, see for example WQ2020201318A1 , WO20141 18236 and US1 1034748B2, which are all hereby incorporated herein by reference in their entirety.In some embodiments, an antigen-binding molecule e.g., TCR described herein comprises a TCRa chain variable domain having less than 82% sequence identity with an alpha chain amino acid sequence disclosed in US1 1034748B2. For example, an antigen-binding molecule e.g., TCR described herein may comprise a TCRa chain variable domain having less than 82%, less than 81%, or less than 80% sequence identity with the entire sequence of SEQ ID NO:7 from US1 1034748B2. In some embodiments, an antigen-binding molecule e.g., TCR described herein does not comprise a TCRa chain variable domain having at least 80%, at least 81 % or at least 82% sequence identity with the entire sequence of SEQ ID NO:7 from US1 1034748B2.In some embodiments, an antigen-binding molecule e.g., TCR described herein comprises a TCR0 chain variable domain having less than 80% sequence identity with a beta chain amino acid sequence disclosed in US1 1034748B2. For example, an antigen-binding molecule e.g., TCR described herein may comprise a TCRfJ chain variable domain having: less than 30% sequence identity with SEQ ID NO:1 from US1 1034748B2, less than 80% sequence identity with SEQ ID NO:5 from US1 1034748B2, less than 30% sequence identity with SEQ ID NO:9 from US1 1034748B2, less than 33% sequence identity with SEQ ID NO: 13 from US1 1034748B2, and / or less than 34% sequence identity with SEQ ID NO: 17 from US1 1034748B2. In some embodiments, an antigen-binding molecule e.g., TCR described herein does not comprise a TCR chain variable domain having: at least 30% sequence identity with SEQ ID NO:1 from US1 1034748B2, at least 80% sequence identity with SEQ ID NO:5 from US1 1034748B2, at least 30% sequence identity with SEQ ID NO:9 from US1 1034748B2, at least 33% sequence identity with SEQ ID NO:13 from US1 1034748B2, and / or at least 34% sequence identity with SEQ ID NO:17 from US1 1034748B2.In some embodiments, the antigen-binding molecule e.g., TCR described herein comprises a CDR30 chain having less than 92% sequence identity with a beta chain amino acid sequence disclosed in any one of US17046581 , EP18893460, US17397841 and PCT / US2021 / 042326. For example, an antigen binding molecule e.g., TCR described herein may comprise a CDR30 chain having less than 92% sequence identity to CASSGGGAEAFF in Table 6 on page 153 of US 17046581 , less than 92% sequence identity to SEQ ID NQ:10361 1 and / or SEQ ID NQ:104085 in EP18893460, less than 92% sequence identify to SEQ ID NO: 602 in US17397841 , and / or less than 92% sequence identity to CASSLGGAEAFF in Table 1 A-03 of PCT / US2021 / 042326.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A10 peptide, e.g., when presented by a major histocompatibility complex(MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by HLA- A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A10 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by a HLA- A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, the antigen-binding molecule is capable of binding to a MAGE-A10-derived antigenic peptide presented through another HLA-A*02 allele, including but not restricted to: HLA- A*02:02, HLA-A*02:03, HLA-A*02:04, HLA-A*02:05, HLA-A*02:06, HLA-A*02:07, HLA-A*02:11 , HLA- A*02:12, HLA-A*02:19, HLA-A*02:24, HLA-A*02:264, or HLA-A*02:52.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A10 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by HLA- A*24. That is, when presented on HLA-A*24.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a MAGE-A10 peptide, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by a HLA- A*24:02 allele. That is, when presented on HLA-A*24:02.In some embodiments, the antigen-binding molecule is capable of binding to a MAGE-A10-derived antigenic peptide presented through another HLA-A*24 allele, including but not restricted to: HLA- A*24:03, sister serotype HLA-A*23 (e.g., HLA-A*23:01 ) or broader serotype group HLA-A9.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:225 or 226, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by HLA-A*02 (also known as HLA-A2, HLA-A02, and HLA-A*2). That is, when presented on HLA-A*02.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:225 or 226, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by a HLA-A*02:01 allele. That is, when presented on HLA-A*02:01.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:227 or 228, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by HLA-A*24. That is, when presented on HLA-A*24.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to SEQ ID NO:227 or 228, e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide) encoded by a HLA-A*24:02 allele. That is, when presented on HLA-A*24:02.Table 1 below provides exemplary antigen specificity, peptide specificity and HLA restriction of TCRs A0385, A0390, A0398, A0409, A0425, A0435 and A0436 disclosed herein.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a GLYDGMEHL (SEQ ID NO:225)-HLA-A*02 complex. The antigen-binding molecule may be TCR A0385, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a GLYDGMEHL (SEQ ID NQ:225)-HLA-A*02:01 complex. The antigen-binding molecule may be TCR A0385, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A- D. In some embodiments, TCR A0385 comprises at least one, some or all of the sequences presented in Row 10 of Table A, Row 10 of Table B, Row 10 of Table C and / or is encoded by one or more sequences in Rows 19 and 20 of Table D.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a SLLKFLAKV (SEQ ID NQ:226)-HLA-A*02 complex. The antigen-binding molecule may be TCR A0390, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0398, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0409, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0435, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0436, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a SLLKFLAKV (SEQ ID NQ:226)-HLA-A*02:01 complex. The antigen-binding molecule may be TCR A0390, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0398, comprising any combination of CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0409, comprising any combination of CDR, FR and / or variable domain sequences as described above and in Tables A-D. The antigen-binding molecule may be TCR A0435, comprising any combination of CDR, FR and / or variable domain sequences asdescribed above and in Tables A-D. The antigen-binding molecule may be TCR A0436, comprising any combination of CDR, FR and / or variable domain sequences as described above and in Tables A-D.In some embodiments, TCR A0390 comprises at least one, some or all of the sequences presented in Row 11 of Table A, Row 11 of Table B, Row 11 of Table C and / or is encoded by one or more sequences in Rows 21 and 22 of Table D. In some embodiments, TCR A0398 comprises at least one, some or all of the sequences presented in Row 12 of Table A, Row 12 of Table B, Row 12 of Table C and / or is encoded by one or more sequences in Rows 23 and 24 of Table D. In some embodiments, TCR A0409 comprises at least one, some or all of the sequences presented in Row 13 of Table A, Row 13 of Table B, Row 13 of Table C and / or is encoded by one or more sequences in Rows 25 and 26 of Table D. In some embodiments, TCR A0435 comprises at least one, some or all of the sequences presented in Row 15 of Table A, Row 15 of Table B, Row 15 of Table C and / or is encoded by one or more sequences in Rows 29 and 30 of Table D. In some embodiments, TCR A0436 comprises at least one, some or all of the sequences presented in Row 16 of Table A, Row 16 of Table B, Row 16 of Table C and / or is encoded by one or more sequences in Rows 31 and 32 of Table D.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a NYEDHFPLL (SEQ ID NO:227)-HLA-A*24 complex. The antigen-binding molecule may be TCR A0425, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a NYEDHFPLL (SEQ ID NO:227)-HLA-A*24:02 complex. The antigen-binding molecule may be TCR A0425, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A- D. In some embodiments, TCR A0425 comprises at least one, some or all of the sequences presented in Row 14 of Table A, Row 14 of Table B, Row 14 of Table C and / or is encoded by one or more sequences in Row 27 (and optionally Row 28) of Table D.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a NYEDHFPLLF (SEQ ID NO:228)-HLA-A*24 complex. The antigen-binding molecule may be TCR A0425, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D. In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a NYEDHFPLLF (SEQ ID NO:228)-HLA-A*24:02 complex. The antigen-binding molecule may be TCR A0425, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A- D. In some embodiments, TCR A0425 comprises at least one, some or all of the sequences presented in Row 14 of Table A, Row 14 of Table B, Row 14 of Table C and / or is encoded by one or more sequences in Row 27 (and optionally Row 28) of Table D.In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of GLYDGMEHL (SEQ ID NO:225). The antigen-binding molecule may be TCR A0385, comprising any combination of relevantCDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 10 in Tables A, B, and / or C, and encoded by one or more sequences in rows 19 and 20 of Table D).In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of SLLKFLAKV (SEQ ID NO:226). The antigen-binding molecule may be TCR A0390, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 11 in Tables A, B, and / or C, and encoded by one or more sequences in rows 21 and 22 of Table D). The antigen-binding molecule may be TCR A0398, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 12 in Tables A, B, and / or C, and encoded by one or more sequences in rows 23 and 24 of Table D). The antigen-binding molecule may be TCR A0409, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 13 in Tables A, B, and / or C, and encoded by one or more sequences in rows 25 and 26 of Table D). The antigen-binding molecule may be TCR A0435, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 15 in Tables A, B, and / or C, and encoded by one or more sequences in rows 29 and 30 of Table D). The antigen-binding molecule may be TCR A0436, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A- D (e.g., in row 16 in Tables A, B, and / or C, and encoded by one or more sequences in rows 31 and 32 of Table D).In some embodiments, an antigen-binding molecule as described herein, e.g., a TCR or fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by a HLA-A*24 allele (e.g., HLA-A*24:02), and a peptide comprising or consisting of NYEDHFPLL (SEQ ID NO:227) or NYEDHFPLLF (SEQ ID NO:228). The antigen-binding molecule may be TCR A0425, comprising any combination of relevant CDR, FR and / or variable domain sequences as described above and in Tables A-D (e.g., in row 14 in Tables A, B, and / or C, and encoded by one or more sequences in rows 27 (and optionally 28) of Table D).The TCRs according to the present disclosure may be synthetic / artificial TCRs comprising TCRa and TCRp human variable regions and mouse constant regions, for example to improve the expression of the TCR, and in order to use the mouse constant region for the tracking of transfected human T cells with an anti-mouse antibody.Provided are human / mouse hybrid TCRs comprising mouse TCRa and TCRb constant region amino acid sequences of SEQ ID NO:167 and SEQ ID NO:168, respectively. Provided herein are also TCRs, e.g., synthetic or artificial TCRs, comprising TCRa and TCRp human variable regions and human constant regions. In some embodiments the human TCRa constant region is shown in SEQ ID NO: 162. In some embodiments the human TCRP constant region is shown in SEQ ID NO: 163 or 164.In some embodiments, the TCR is a hybrid TCR construct. In some embodiments, the TCR comprises a human TCRa variable domain amino acid sequence and a mouse TCRa constant region. In some embodiments, the TCR comprises a human TCRp variable domain amino acid sequence and a mouse TCRp constant region. In some embodiments, the TCR comprises: (i) a human TCRa variable domain amino acid sequence and a mouse TCRa constant region; in combination with (ii) a human TCRp variable domain amino acid sequence and a mouse TCRp constant region.In some embodiments, the TCRa constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, >80%, £85%, £86%, £87%, >88%, £89%, £90%, >91 %, £92%, £93%, 94%, >95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 167. In some embodiments, the TCRp constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:168. It will be appreciated that such TCR constructs may further comprise any of the TCR variable domains described herein, e.g., human variable domains.In some embodiments, the TCR is a fully human TCR construct. In some embodiments, the TCR comprises a human TCRa variable domain amino acid sequence and a human TCRa constant region. In some embodiments, the TCR comprises a human TCRp variable domain amino acid sequence and a human TCRp constant region. In some embodiments, the TCR comprises: (i) a human TCRa variable domain amino acid sequence and a human TCRa constant region; in combination with (ii) a human TCRp variable domain amino acid sequence and a human TCRp constant region.In some embodiments, the TCRa constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 162 or 165. In some embodiments, the TCRp constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:163, 164, or 166. It will be appreciated that such TCR constructs may further comprise any of the TCR variable domains described herein, e.g., human variable domains.In some embodiments, the TCRa constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 162. In some embodiments, the TCRp constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:163 or 164. It will be appreciated thatsuch TCR constructs may further comprise any of the TCR variable domains described herein, e.g., human variable domains.In some embodiments, any TCRa polypeptide / domain / chain and / or TCRp polypeptide / domain / chain described herein may comprise modifications to promote stable expression and / or reduce mismatching with endogenous TCR chains.In some embodiments, any TCRa chain described herein may comprise a constant region comprising a cysteine residue at the amino acid position corresponding to position 48 of SEQ ID NO:162. In some embodiments, any TCRp chain described herein may comprise a constant region comprising a cysteine residue at the amino acid position corresponding to position 57 of SEQ ID NO: 163 or 164. In some embodiments, any TCRa chain described herein may comprise a TCRa constant region comprising a cysteine residue at the amino acid position corresponding to position 48 of SEQ ID NO: 162 and a TCRp constant region comprising a cysteine residue at the amino acid position corresponding to position 57 of SEQ ID NO:163 or 164.In some embodiments, any TCRa chain described herein may comprise a constant region comprising a mutated version of the human TCRa constant region as in SEQ ID NO: 165. In some embodiments, any TCRp chain described herein may comprise a constant region comprising a mutated version of the human TCRp constant region as in SEQ ID NO:166. In some embodiments, any TCR described herein may comprise a human TCR constant region comprising a mutated version of the human TCRa constant region as in SEQ ID NO:165 and a mutated version of human TCRp constant region as in SEQ ID NO: 166. The mutation comprises the introduction of a Cys in both the alpha and beta chains of the TCR to create a stabilizing disulfide bridge between the two chains. TCR chains were modified by mutagenesis of residue 48 in the Ca region from Thr to Cys and residue 57 of the CP region from Ser to Cys. The method has been described previously in Kuball et al, Blood. 2007 Mar 15; 109(6): 2331-2338., which is hereby incorporated by reference in its entirety. The mutation promotes stable expression and pairing of the transduced TCR in human T cells in which the endogenous TCR is not knocked out.In some embodiments, an antigen-binding molecule according to the present disclosure, e.g., TCR or fragment thereof, comprises a TCRa chain comprising a TCRa constant region having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence selected from: SEQ ID NO:165, 162 and 167; and a TCRP chain comprising a TCRp constant region having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence selected from: SEQ ID NO: 166, 163, 164 and 168.In some embodiments, an antigen-binding molecule according to the present disclosure, e.g., TCR or fragment thereof, comprises a TCRa chain comprising a TCRa constant region having at least 80%, 85%, 90%, or 95% sequence identity to SEQ ID NO: 165, and a TCRp chain comprising a TCRp constant region having at least 80%, 85%, 90%, or 95% sequence identity to SEQ ID NO: 166.In some embodiments, an antigen-binding molecule according to the present disclosure, e.g., TCR or fragment thereof, comprises a TCRa chain comprising a TCRa constant region having at least 80%, 85%,90%, or 95% sequence identity to SEQ ID NO: 162, and a TCR0 chain comprising a TCR0 constant region having at least 80%, 85%, 90%, or 95% sequence identity to SEQ ID NO: 163 or 164.The TCRs / antigen-binding molecules described herein may be comprised within multispecific molecules. That is, the present invention provides a multispecific antigen-binding molecule comprising an antigenbinding molecule e.g., a TCR or an antigen-binding fragment thereof described herein. A multispecific antigen-binding molecule may be e.g., bispecific, trispecific, etc. Also provided is the use of a TCR / antigen-binding molecule described herein as part of a fusion construct, wherein said fusion construct comprises a TCR / antigen-binding molecule described herein and an antigen-binding molecule that is capable of binding to a molecule expressed (e.g., specifically expressed) by immune cells, e.g., T cells, including but not limited to CD3.In some embodiments, a multispecific antigen-binding molecule according to the present disclosure comprises an antigen-binding molecule e.g., a TCR or an antigen-binding fragment thereof described herein and at least one further antigen-binding molecule that is capable of binding to a molecule expressed by an immune cell. The two or more antigen-binding molecules may be expressed / presented as a fusion construct or fusion protein.In some embodiments, a multispecific antigen-binding molecule according to the present disclosure comprises an antigen-binding molecule e.g., a TCR or an antigen-binding fragment thereof described herein and at least one further antigen-binding molecule that is capable of binding to a molecule expressed by a T cell. The molecule expressed by an immune cell / a T cell may be CD3. The molecule expressed by an immune cell / a T cell may be CD4 or CD8. That is, the TCRs / antigen-binding molecules described herein may be used in bispecific T cell engagers (BiTEs) or T cell Engaging Receptors (TCER®). Such multispecific molecules can target immune cells, e.g., via a CD3-binding arm, to diseased cells that are recognised via the TCR moiety.In some embodiments, the TCR / antigen-binding molecule described herein and / or the at least one further antigen-binding molecule that is capable of binding to a molecule expressed by an immune cell are single-chain molecules, e.g., in scFv form. The at least two antigen-binding molecules may be connected via a linker.The antigen-binding molecules / TCRs / TCR chains / TCR fragments described herein may be characterised by reference to certain functional properties. In some embodiments, an article described herein may possess one or more of the following properties: binds to an antigen (e.g., an antigen according to the present disclosure); binds to an antigen-derived peptide (e.g., an antigenic peptide); binds to WT-1 ; binds to a WT-1 -derived peptide (e.g., an antigenic peptide); binds to VLDFAPPGA (SEQ ID NO:1 ); binds to VLDFX1PPX2X3 (SEQ ID NO: 179); binds to VLDFX1X2PX3X4 (SEQ ID NO: 180);binds to VX1DFX2X3PX4X5 (SEQ ID N0:181); binds to VLDFX1PX2GX3 (SEQ ID NO: 182); binds to a WT-1 -derived peptide (e.g., an antigenic peptide) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to VLDFAPPGA (SEQ ID NO: 1 ) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to VLDFX1PPX2X3 (SEQ ID NO: 179) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to VLDFX1X2PX3X4 (SEQ ID NO: 180) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to VX1DFX2X3PX4X5 (SEQ ID NO:181 ) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to VLDFX1PX2GX3 (SEQ ID NO: 182) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell expressing WT-1 ; binds to a cell expressing a WT-1 -derived peptide (e.g., an antigenic peptide); binds to a cell presenting VLDFAPPGA (SEQ ID NO:1 ), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting VLDFX1PPX2X3 (SEQ ID NO: 179), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting VLDFX1X2PX3X4 (SEQ ID NO: 180), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting VX1DFX2X3PX4X5 (SEQ ID NO:181 ), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting VLDFX1PX2GX3 (SEQ ID NO:182), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to MAGE-A1 ; binds to a MAGE-A1 peptide (e.g., antigenic peptide); binds to KVLEYVIKV (SEQ ID NO:191 ); binds to KXIX2EX3VIX4X5 (SEQ ID NO:223);binds to a MAGE-A1 peptide (e.g., antigenic peptide) when presented by a major histocompatibility complex (MHO) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to KVLEYVIKV (SEQ ID NO:191 ) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to KXIX2EX3VIX4X5 (SEQ ID NO:223) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell expressing MAGE-A1 ; binds to a cell expressing a MAGE-A1 peptide; binds to a cell presenting KVLEYVIKV (SEQ ID NO: 191 ), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting KX1X2EX3VIX4X5 (SEQ ID NO:223), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to MAGE-A10; binds to a MAGE-A10 peptide (e.g., antigenic peptide); binds to GLYDGMEHL (SEQ ID NO:225); binds to SLLKFLAKV (SEQ ID NO:226); binds to NYEDHFPLL (SEQ ID NO:227); binds to NYEDHFPLLF (SEQ ID NO:228); binds to a MAGE-A10 peptide (e.g., antigenic peptide) when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to GLYDGMEHL (SEQ ID NO:225) when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to SLLKFLAKV (SEQ ID NO:226) when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to NYEDHFPLL (SEQ ID NO:227) when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*24, e.g., encoded by HLA-A*24:02; binds to NYEDHFPLLF (SEQ ID NO:228) when presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide, e.g., encoded by HLA-A*24, e.g., encoded by HLA-A*24:02; binds to a cell expressing MAGE-A10; binds to a cell expressing a MAGE-A10 peptide;binds to a cell presenting GLYDGMEHL (SEQ ID NO:225), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting SLLKFLAKV (SEQ ID NO:226), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*02, e.g., encoded by HLA-A*02:01 ; binds to a cell presenting NYEDHFPLL (SEQ ID NO:227), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*24, e.g., encoded by HLA-A*24:02; binds to a cell presenting NYEDHFPLLF (SEQ ID NO:228), e.g., when presented by a major histocompatibility complex (MHC) molecule comprising a polypeptide (e.g., a MHC class I a chain polypeptide), e.g., encoded by HLA-A*24, e.g., encoded by HLA-A*24:02; activates a host cell, e.g., T cell, in which the article is comprised / expressed; promotes cell killing activity of a cell in which the article is comprised / expressed; has an ‘anti-cancer’ effect when comprised / expressed in a host cell, e.g., T cell; has an ‘anti-tumour’ effect when comprised / expressed in a host cell, e.g., T cell; confers cytotoxic activity when comprised / expressed in a host cell, e.g., T cell; and / or promotes IFNy secretion from a host cell, e.g., T cell, in which it is comprised / expressed.It will be appreciated that a given antigen-binding molecule may display more than one of the properties recited in the preceding paragraph. A given antigen-binding molecule may be evaluated for the properties recited in the preceding paragraph using suitable assays. For example, the assays may be e.g., in vitro assays, optionally cell-based assays or cell-free assays. In some embodiments, the assays may be e.g., in vivo assays, i.e., performed in non-human animals. In some embodiments, the assays may be e.g., ex vivo assays, i.e., performed using cells / tissue / an organ obtained from a subject.Where assays are cell-based assays, they may comprise treating cells with a given host cell comprising / expressing the antigen-binding molecule / TCR in order to determine whether the host cells / antigen-binding molecule / TCR displays one or more of the recited properties. Assays may employ species labelled with detectable entities in order to facilitate their detection. Assays may comprise evaluating the recited properties following treatment of cells separately with a range of quantities / concentrations of a given host cell / antigen-binding molecule / TCR (e.g., a dilution series). It will be appreciated that the cells preferably express the target antigen for the antigen-binding molecule / TCR (i.e., a WT-1 -derived peptide, such as those described herein).The ability of an antigen-binding molecule to bind specifically to a given molecule / complex can be determined by analysis according to methods known in the art, such as by ELISA, Surface Plasmon Resonance (SPR; see e.g., Hearty et al., Methods Mol Biol (2012) 907:411-442), Bio-Layer Interferometry (BLI; see e.g., Lad et al., (2015) J Biomol Screen 20(4): 498-507), flow cytometry, or by a radiolabelled antigen-binding assay (RIA) enzyme-linked immunosorbent assay. Through such analysis binding to a given molecule can be measured and quantified. In some embodiments, the binding may be the response detected in a given assay.The term ‘binds to’ or ‘specifically binds,’ as used herein with respect to a T cell receptor, refers to a T cell receptor which recognizes a specific antigen:MHC complex, but does not substantially recognize or bind other antigemMHC complexes in a sample.Cell killing can be investigated, for example, using any of the methods reviewed in Zaritskaya et al., Expert Rev Vaccines (2011 ), 9(6):601-616, hereby incorporated by reference in its entirety. Examples of in vitro assays of cytotoxicity / cell killing assays include release assays such as the51Cr release assay, the lactate dehydrogenase (LDH) release assay, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) release assay, ATP release assay using Cell Titre Gio, and the calcein-acetoxymethyl (calcein-AM) release assay. These assays measure cell killing based on the detection of factors released from lysed cells.An ‘anti-cancer effect' as used herein, refers to a biological effect that can present as an increase in killing of cancer cells, a decrease in the number of cancer cells, a decrease in cancer cell proliferation, a decrease in the number / volume of metastases, an increase in overall or progression-free survival, an increase in life expectancy or amelioration of various physiological symptoms associated with the cancer. An anti-cancer effect can also refer to the prevention of the occurrence of a cancer, e.g., a vaccine.An ‘anti-tumor effect’ as used herein, refers to a biological effect that can present as an increase in killing of tumor cells, a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in tumor cell proliferation, a decrease in the number of metastases, an increase in overall or progression-free survival, an increase in life expectancy, or amelioration of various physiological symptoms associated with the tumor. An anti-tumor effect can also refer to the prevention of the occurrence of a tumor, e.g., a vaccine.An antigen-binding molecule of the present disclosure may be analysed for the properties described in the preceding paragraph in appropriate assays. Such assays include e.g., in vivo models.In some embodiments, the functionality of TCRs can be assessed by quantification of cytokine secretion in the cell culture media.It is well known that cytokines and their signaling pathways exert potent effects on T cell activation, differentiation, and function. Interferon gamma (IFNy) is crucial for Th1 differentiation and induction of IFN-y release. In other subsets, IFN-y inhibits the differentiation of Th2 and Th17 cells but has been shown to promote Regulatory T cells (Tregs) and antigen-specific memory T cell generation (Bishop et al. Front Immunol. 2021 Apr 13). IFNy is a key moderator of cell-mediated immunity with diverse, mainly pro- inflammatory actions on immunocytes and target tissue. Recent studies have shown it may enhance antitumor and antiviral effects of CD8 T cells. IFNy is released in large amounts by macrophages, activated CD8 T cells, natural killer T cells, and Th1 CD4 T cells (Bhat et al. Cell Death Dis. 2017 Jun1 ;8(6):e2836). IFNy secreted by T cells into the culture medium during the cytotoxicity assay can be quantified by ELISA methodology.The functionality of TCRs of the present disclosure can be assessed using primary human T cells transduced with said TCRs.Peripheral blood mononuclear cells (PBMCs) from healthy donors can be used as a source of primary T cells for the preparation of effector cells, e.g., as described herein. Transduction efficiency can be verified by flow cytometry, e.g., using an anti-mouse TCR antibody to verify that at least 50% of T cells express the transduced TCR.The functionality of TCRs can be assessed by quantification of cytotoxicity using a flow cytometry assay, e.g., as described herein. For example, TCR-expressing T cells can be used as effector cells and can be mixed with cells expressing the target peptide (target cells).The functionality of TCRs can also be assessed by quantification of cytotoxicity, e.g., using xCelligence impedance readout as described herein.Nucleic acids and vectorsAny antigen-binding molecule, e.g., TCR, multispecific antigen-binding molecule or fragment thereof, according to the present disclosure may be encoded by any nucleotide sequence that encodes for the required amino acid sequence(s), taking into account codon degeneracy.The present disclosure provides nucleic acids, or a plurality of nucleic acids, encoding the TCRs, antigenbinding molecules, polypeptides and polypeptide complexes according to the present disclosure. In some embodiments, the nucleic acid(s) comprise or consist of DNA and / or RNA. In some embodiments, the nucleic acid is a polynucleotide, e.g., a polydeoxyribonucleotide or a polyribonucleotide.An antigen-binding molecule or polypeptide according to the present disclosure may be produced within a cell by translation of RNA encoding the polypeptide(s). An antigen-binding molecule or polypeptide according to the present disclosure may be produced within a cell by transcription from nucleic acid encoding the polypeptide(s), and subsequent translation of the transcribed RNA.In some embodiments, the nucleic acid(s) may be, or may be comprised / contained in, a vector, or a plurality of vectors.Accordingly, the present disclosure also provides vectors, plasmids, and a plurality of vectors and / or plasmids containing nucleic acids, or a plurality of nucleic acids, according to the present disclosure. Nucleic acids, nucleotide sequences, plasmids and vectors according to the present disclosure may be provided in purified or isolated form, i.e., from other nucleic acids, plasmids, vectors or naturally-occurring biological material.Provided herein is a nucleotide sequence encoding a TCRa variable domain according to the present disclosure. In some embodiments, the nucleotide sequence encoding a TCRa variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, 80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequenceidentity, with the nucleotide sequence of SEQ ID NO:76, 92, 68, 84, 66, 82, 70, 86, 72, 88, 74, 90, 78, 94, 80, 96, 200, 202, 285, 299, 287, 301 , 289, 303, 291 , 305, 293, 307, 295, 309, 297 or 311. In some embodiments, the nucleotide sequence encoding a TCRa variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO: 76 or 92. In some embodiments, the nucleotide sequence encoding a TCRa variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:68 or 84.Provided herein is a nucleotide sequence encoding a TCRP variable domain according to the present disclosure. In some embodiments, the nucleotide sequence encoding a TCRP variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:77, 93, 69, 85, 67, 83, 71 , 87, 73, 89, 75, 91 , 79, 95, 81 , 97, 201 , 203, 286, 300, 288, 302, 290, 304, 292, 306, 294, 308, 296, 310, 298 or 312. In some embodiments, the nucleotide sequence encoding a TCRP variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:77 or 93. In some embodiments, the nucleotide sequence encoding a TCRP variable domain has at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:69 or 85.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a polypeptide or polypeptides encoded by a nucleic acid / nucleotide sequence described herein.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:76, 92, 68, 84, 66, 82, 70, 86, 72, 88, 74, 90, 78, 94, 80, 96, 200, 202, 285, 299, 287, 301 , 289, 303, 291 , 305, 293, 307, 295, 309, 297 or 311 . In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:76 or 92. In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:68 or 84.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:77, 93, 69, 85, 67, 83, 71 , 87, 73, 89, 75, 91 , 79, 95, 81 , 97, 201 , 203, 286, 300, 288, 302, 290, 304, 292, 306, 294, 308, 296, 310, 298 or 312. In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:77 or 93. In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:69 or 85.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (I) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:76, 92, 68, 84, 66, 82, 70, 86, 72, 88, 74, 90, 78, 94, 80, 96, 200, 202, 285, 299, 287, 301 , 289, 303, 291 , 305, 293, 307, 295, 309, 297 or 311 ; in combination with (ii) a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:77, 93, 69, 85, 67, 83, 71 , 87, 73, 89, 75, 91 , 79, 95, 81 , 97, 201 , 203, 286, 300, 288, 302, 290, 304, 292, 306, 294, 308, 296, 310, 298 or 312.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (I) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the TCRa variable domain encoded by a nucleotide sequence as indicated in Column A of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 or 32 of Table D; in combination with (ii) a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the TCRp variable domain encoded by a nucleotide sequence as indicated in Column B of row 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 or 32 of Table D; wherein the nucleotide sequence encoding the TCRa variable domain from Column A and the nucleotide sequence encoding the TCRp variable domain from Column B are selected from the same row.By way of illustration, in some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (i) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, >80%, £85%, £86%, £87%, >88%, £89%, £90%, >91 %, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:92 (row 12); and (ii) a TCR variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:93 (row 12).By way of further illustration, in some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (i) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO: 84 (row 4); and (ii) a TCR0 variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91 %, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:85 (row 4).In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (i) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of as indicated in Column A of row 1 , 3, 5, 7, 9, 1 1 , 13, 15, 17, 19, 21 , 23, 25, 27, 29 or 31 of Table D; in combination with (ii) a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the TCRp variable domain encoded by a nucleotide sequence as indicated in Column B of row 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 or 32 of Table D, respectively.In some embodiments, the antigen-binding molecule, e.g., TCR, of the present disclosure comprises: (i) a TCRa variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of as indicated in Column A of row 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 or 32 of Table D; in combination with (ii) a TCRp variable domain encoded by a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the TCRp variable domain encoded by a nucleotide sequence as indicated in Column B of row 1 , 3, 5, 7, 9, 1 1 , 13, 15, 17, 19, 21 , 23, 25, 27, 29 or 31 of Table D, respectively.Any of the nucleotide sequences described herein may be replaced by a codon degenerate nucleotide sequence thereof encoding the amino acid sequence encoded by the reference sequence.As used herein, the term ‘nucleic acid’ refers to a polymer comprising multiple nucleotide monomers (e.g., ribonucleotide monomers or deoxyribonucleotide monomers). ‘Nucleic acid’ includes, for example, genomic DNA, cDNA, RNA, and DNA-RNA hybrid molecules. Nucleic acid molecules can be naturally occurring, recombinant, or synthetic. In addition, nucleic acid molecules can be single- stranded, doublestranded or triple- stranded. In some embodiments, nucleic acid molecules can be modified. In the case of a double-stranded polymer, ‘nucleic acid’ can refer to either or both strands of the molecule.The term ‘nucleotide sequence,’ in reference to a nucleic acid, refers to a contiguous series of nucleotides that are joined by covalent linkages, such as phosphorus linkages (e.g., phosphodiester, alkyl and aryl- phosphonate, phosphorothioate, phosphotriester bonds), and / or non-phosphorus linkages (e.g., peptide and / or sulfamate bonds).The terms ‘nucleotide’ and ‘nucleotide monomer’ refer to naturally occurring ribonucleotide or deoxyribonucleotide monomers, as well as non-naturally occurring derivatives and analogs thereof. Accordingly, nucleotides can include, for example, nucleotides comprising naturally occurring bases (e.g., adenosine, thymidine, guanosine, cytidine, uridine, inosine, deoxyadenosine, deoxythymidine, deoxyguanosine, or deoxycytidine) and nucleotides comprising modified bases known in the art.Where a nucleotide sequence is disclosed herein, the reverse complement thereof is also expressly contemplated. Moreover, in each instance wherein a nucleotide sequence is disclosed herein, codon degenerate nucleotide sequences thereof encoding the same amino acid sequence are also expressly contemplated. A 'codon degenerate nucleotide sequence’ of a reference nucleotide sequence refers to a nucleotide sequence having a non-identical nucleotide sequence to the nucleotide sequence of the reference nucleotide sequence, but encoding the same amino acid sequence as the amino acid sequence encoded by the reference nucleotide sequence, as a consequence of degeneracy of the genetic code.‘Encoding’ refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides ( / .e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the noncoding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.Unless otherwise specified, a 'nucleotide sequence encoding an amino acid sequence’ includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase ‘nucleotide sequence that encodes a protein or an RNA’ may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).In various embodiments, a nucleotide sequence according to the present disclosure encoding one or more antigen-binding molecules or polypeptides of the TCR is codon optimized, e.g., for expression in achosen cell, such as a mammalian cell. The mammalian cell may be an immune cell, such as a T cell, e.g., a human T cell.Codon optimization is a common method used to increase the expression of recombinant proteins, especially in the field of biotherapeutics. Its basis lies in the use of synonymous codon mutations in messenger RNA (mRNA) coding regions. Codon optimization is known to maximize protein expression by overcoming expression limitations associated with codon usage. This routine method has been reported to increase protein expression by up to >1 OOO-fold. This method is often applied in order to fine-tune the expression of one of two light chain genes of a bispecific antibody (Mauro, BioDrugs 32;69-81 (2018)).Altering codon usage is possible since the 20 amino acids are encoded by 61 codons. Except for methionine and tryptophane, which are encoded by a single codon each, all other amino acids are specified by two to six redundant codons. Synonymous codon usage is not random, as it varies between different organisms, between different tissues of the same organism, and even between different parts of the same gene (Mauro, BioDrugs 32;69-81 (2018)).Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, £98%, 99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:92, 84,82, 86, 88, 90, 94, 96, 202, 299, 301 , 303, 305, 307, 309 or 311 . Said nucleotide sequences encode TCRa variable domains and are codon-optimised sequences derived from SEQ ID NO:76, 68, 66, 70, 72, 74, 78, 80, 200, 285, 287, 289, 291 , 293, 295 and 297, respectively. That is, SEQ ID NO:76, 68, 66, 70, 72, 74, 78, 80, 200, 285, 287, 289, 291 , 293, 295 and 297 are codon-optimised to produce SEQ ID NO:92, 84, 82, 86, 88, 90, 94, 96, 202, 299, 301 , 303, 305, 307, 309 and 311 , respectively.Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:92. Said nucleotide sequence encodes a TCRa variable domain and is a codon-optimised sequence derived from SEQ ID NO:76. That is, SEQ ID NO:76 is codon-optimised to produce SEQ ID NO:92.Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:84. Said nucleotide sequence encodes a TCRa variable domain and is a codon-optimised sequence derived from SEQ ID NO:68. That is, SEQ ID NO:68 is codon-optimised to produce SEQ ID NO:84.Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:93, 85,83, 87, 89, 91 , 95, 97, 203, 300, 302, 304, 306, 308, 310 or 312. Said nucleotide sequences encode TCRp variable domains and are codon-optimised sequences derived from SEQ ID NO:77, 69, 67, 71 , 73, 89, 91 , 79, 81 , 201 , 286, 288, 290, 292, 294, 296 and 298, respectively. That is, SEQ ID NO:77, 69, 67, 71 , 73, 89, 91 , 79, 81 , 201 , 286, 288, 290, 292, 294, 296 or 298 are codon-optimised to produce SEQ ID NO:93, 85, 83, 87, 89, 91 , 95, 97, 203, 300, 302, 304, 306, 308, 310 or 312, respectively.Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of £75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:93. Said nucleotide sequence encodes a TCRp variable domain and is a codon-optimised sequence derived from SEQ ID NO:77. That is, SEQ ID NO:77 is codon-optimised to produce SEQ ID NO:93.Provided herein is a nucleotide sequence having at least 70% nucleotide sequence identity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, £98%, £99% or 100% nucleotide sequence identity, with the nucleotide sequence of SEQ ID NO:85. Said nucleotide sequence encodes a TCRp variable domain and is a codon-optimised sequence derived from SEQ ID NO:69. That is, SEQ ID NO:69 is codon-optimised to produce SEQ ID NO:85.In some embodiments, a TCR according to the present disclosure may be expressed as a hybrid TCR construct. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising a human TCRa variable domain amino acid sequence and a mouse TCRa constant region. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising a human TCRp variable domain amino acid sequence and a mouse TCRp constant region. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising (I) a human TCRa variable domain amino acid sequence and a mouse TCRa constant region; in combination with (ii) a human TCRp variable domain amino acid sequence and a mouse TCRp constant region.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 167. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRp constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:168.In some embodiments, a TCR according to the present disclosure may be expressed as a fully human TCR construct. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising a human TCRa variable domain amino acid sequence and a human TCRa constant region. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising a human TCRp variable domain amino acid sequence and a human TCRp constant region. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct comprising (I) a human TCRa variable domain amino acid sequence and a human TCRa constant region; in combination with (ii) a human TCRp variable domain amino acid sequence and a human TCRp constant region.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises an amino acid having at least 70% amino acid sequenceidentity, e.g., one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, £95%, £96%, £97%, >98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 162 or 165. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCR constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91 %, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 163, 164, or 166.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO: 162. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCR0 constant region comprises an amino acid having at least 70% amino acid sequence identity, e.g., one of £75%, £80%, £85%, £86%, £87%, £88%, £89%, £90%, £91%, £92%, £93%, £94%, £95%, £96%, £97%, £98%, £99% or 100% amino acid sequence identity, with the amino acid sequence of SEQ ID NO:163 or 164.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa polypeptide / domain / chain and / or TCR polypeptide / domain / chain comprise a modification(s) capable of promoting stable expression of the TCR and / or reducing mismatching with endogenous TCR polypeptides / domains / chains.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises a cysteine residue at the amino acid position corresponding to position 48 of SEQ ID NO: 162. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCR0 constant region comprises a cysteine residue at the amino acid position corresponding to position 57 of SEQ ID NO: 163 or 164. In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises a cysteine residue at the amino acid position corresponding to position 48 of SEQ ID NO: 162 and the TCR constant region comprises a cysteine residue at the amino acid position corresponding to position 57 of SEQ ID NO: 163 or 164.In some embodiments, a TCR according to the present disclosure may be expressed as a TCR construct wherein the TCRa constant region comprises an amino acid having the sequence of SEQ ID NO: 165 and the TCRp constant region comprises an amino acid having the sequence of SEQ ID NO:166.An antigen-binding molecule, TCR or polypeptide according to the present disclosure may be produced within a cell by translation of RNA encoding the relevant polypeptide(s). An antigen-binding molecule, TCR or polypeptide according to the present disclosure may be produced within a cell by transcription from nucleic acid(s) encoding the relevant polypeptide(s), and subsequent translation of the transcribed RNA. Constituent polypeptides of a TCR or antigen-binding molecule according to the present disclosure may be encoded by different nucleic acids or plurality of nucleic acids, or by different vectors or plurality of vectors.In some embodiments, a nucleotide sequence encoding an antigen-binding molecule according to the present disclosure, e.g., a TCR or fragment thereof, is an mRNA.In some embodiments, a nucleotide sequence encoding an antigen-binding molecule according to the present disclosure, e.g., a TCR or fragment thereof, is comprised / contained within a vector or plasmid. That is, the present disclosure provides a vector or plasmid comprising a nucleotide sequence encoding an antigen-binding molecule according to the present disclosure, e.g., a TCR or fragment thereof.As referred to herein, a ‘vector’ may be a nucleic acid molecule used as a vehicle to transfer exogenous nucleic acid into a cell.Accordingly, the present disclosure also provides a vector, or plurality of vectors, comprising the nucleic acid or plurality of nucleic acids according to the present disclosure. The vector may facilitate delivery of the nucleic acid(s) encoding a polypeptide according to the present disclosure to a cell. The vector may be an expression vector comprising elements required for expressing a polypeptide according to the present disclosure. The vector may comprise elements facilitating integration of the nucleic acid(s) into the genomic DNA of cell into which the vector is introduced.A vector may be a vector for expression of the nucleic acid in a cell ( / .e., an expression vector). Vectors may include a promoter sequence operably linked to a nucleotide sequence encoding a TCR / antigen- binding molecule / polypeptide according to the present disclosure. A vector may also include a termination codon ( / .e., 3’ in the nucleotide sequence of the vector to the nucleotide sequence encoding the polypeptide(s)) and expression enhancers. Any suitable vectors, promoters, enhancers and termination codons known in the art may be used to express a peptide or polypeptide from a vector according to the present disclosure.The term ‘operably linked’ may include the situation where nucleic acid encoding a polypeptide according to the present disclosure and regulatory nucleotide sequence(s) (e.g., a promoter and / or enhancers) are covalently linked in such a way as to place the expression of the nucleic acid encoding a polypeptide under the influence or control of the regulatory nucleotide sequence(s) (thereby forming an expression cassette). Thus, a regulatory sequence is operably linked to the selected nucleotide sequence if the regulatory sequence is capable of effecting transcription of the nucleotide sequence. The resulting transcript(s) may then be translated into the desired polypeptide(s).‘Expression vector’ refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai viruses, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide. For example, the expression vector backbone may be the sequence of SEQ ID NO: 171 .Vectors contemplated in connection with the present disclosure include DNA vectors, RNA vectors, plasmids (e.g., conjugative plasmids (e.g., F plasmids), non-conjugative plasmids, R plasmids, col plasmids, episomes), viral vectors (e.g., retroviral vectors, e.g., gammaretroviral vectors (e.g., murineLeukemia virus (MLV)-derived vectors, e.g., SFG vector), lentiviral vectors, adenovirus vectors, adeno- associated virus vectors, vaccinia virus vectors and herpesvirus vectors), transposon-based vectors, and artificial chromosomes (e.g., yeast artificial chromosomes), e.g., as described in Maus et al., Annu Rev Immunol (2014) 32:189-225 and Morgan and Boyerinas, Biomedicines (2016) 4:9, which are both hereby incorporated by reference in their entirety. In some embodiments, a vector according to the present disclosure is a lentiviral vector.In some embodiments, a vector is selected based on tropism for a cell type / tissue / organ to which it is desired to deliver the nucleic acid. In some embodiments, a vector is selected based on tropism for a cell type in which it is desired to express the TCR / antigen-binding molecule / polypeptide(s). For example, it may be desired to deliver the nucleic acid / express the TCR / antigen-binding molecule / polypeptide(s) in an immune cell, e.g., a T cell.In some embodiments, the nucleic acid is a vector suitable for delivering the nucleic acid encoding the antigen-binding molecule / TCR as a gene therapy. In some embodiments, the vector is an adeno- associated virus (AAV) vector. Adeno-associated virus vectors and their use to vector gene therapy is reviewed e.g., in Wang et al., Nat. Rev. Drug Discov. (2019) 18: 358-378 and Li and Samulski, Nat. Rev. Genet. (2020) 12: 255-272, both of which are hereby incorporated by reference in their entirety. In some embodiments, a vector may be an adeno-associated virus vector described in Wang et al., Nat. Rev. Drug Discov. (2019) 18: 358-378. In some embodiments, a vector may be an adeno-associated virus vector described in Li and Samulski, Nat. Rev. Genet. (2020) 12: 255-272.In some embodiments, a vector may be an adeno-associated viral vector of one of the following serotypes: AAV1 , AAV2, AAV2I8, AAV5, AAV6, AAV8, AAV9, AAV9.45, AAV10 or AAVrh74.In some embodiments, a vector may be a lentiviral vector. A ‘lentivirus’ as used herein refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect nondividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses. Vectors derived from lentiviruses offer the means to achieve significant levels of gene transfer in vivo. For example, pALD lentiviral vectors can be obtained from Aldevron / Oxgene.In some embodiments, the vector may be a eukaryotic vector, i.e., a vector comprising the elements necessary for expression of protein from the vector in a eukaryotic cell. In some embodiments, the vector may be a mammalian vector, e.g., comprising a cytomegalovirus (CMV) or SV40 promoter to drive protein expression.In some embodiments, a vector comprises modification to increase binding to and / or transduction of a cell-type of interest (i.e., as compared to the level of binding / transduction by the unmodified vector). In some embodiments modification is to a capsid protein.In some embodiments, a vector comprises a capsid protein comprising a cell-targeting peptide. In some embodiments the cell-targeting peptide is a cell-targeting peptide described in Buning and Srivastava, Molecular Therapy: Methods & Clinical Development (2019) 12: 248-265, which is hereby incorporated by reference in its entirety.In some embodiments, a vector comprises a capsid protein comprising substitution to one or more tyrosine residues, e.g., one or more surface-exposed tyrosine residues. In some embodiments, one or more tyrosine residues of the capsid protein are substituted with phenylalanine. In some embodiments, a vector comprises a capsid protein in which one or more tyrosine residues are substituted with another amino acid as described in lida et al., Biomed Res Int. (2013) 2013: 974819, which is hereby incorporated by reference in its entirety.In some embodiments, a vector may be an adeno-associated virus vector described in Buning and Srivastava, supra. In some embodiments, a vector may be an adeno-associated virus vector described in lida et al., supra.SEQ ID NO: 170 herein provides an exemplary expression vector for the delivery and / or expression of TCR_A0427. SEQ ID NO:370 herein provides an exemplary expression vector for the delivery and / or expression of TCR A0385. In some embodiments, a vector is based on SEQ ID NO: 170 or SEQ ID NO: 171 herein. In some embodiments, any nucleic acid(s) / nucleotide sequence(s) encoding a TCR can be inserted into the backbone of SEQ ID NO: 171 .In some embodiments the nucleic acid / vector comprises one or more sequences for controlling expression of the nucleic acid. Accordingly, in some embodiments the nucleic acid / vector comprises a control element for inducible expression of the nucleic acid.A sequence for controlling expression of the nucleic acid may provide for expression of the nucleic acid by cells of a particular type or tissue. For example, expression may be under the control of a cell type- or tissue-specific promoter. The term ‘promoter’ as used herein is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.Promoters for cell type- or tissue-specific expression of a nucleic acid in accordance with the present invention can be selected in accordance with the disease to be treated / prevented. For example, the promoter may drive expression in an immune cell. The promoter may be a tissue-specific promoter, e.g., which, when operably linked with a polynucleotide encodes or specified by a gene, causes the gene product to be produced in a cell substantially only if the cell is a cell of the tissue type corresponding to the promoter.Expression may be under the control of a constitutive promoter, e.g., a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell.A sequence for controlling expression of the nucleic acid may provide for expression of the nucleic acid in response to e.g., a given agent / signal. For example, expression may be under the control of inducible promoter. The agent may provide for inducible expression of the nucleic acid in vivo by administration of the agent to a subject having been administered with a modified cell according to the disclosure, or ex vivo / in vitro by administration of the agent to cells in culture ex vivo or in vitro.In some embodiments a nucleic acid or vector according to the present disclosure may employ a conditional expression system for controlling expression of the nucleic acid encoding the antigen-binding- molecule / TCR by cells comprising the nucleic acid / vector. 'Conditional expression’ may also be referred to herein as ‘inducible expression’, and refers to expression contingent on certain conditions, e.g., the presence of a particular agent. Conditional expression systems are well known in the art and are reviewed e.g., in Ryding et a / . Journal of Endocrinology (2001 ) 171 , 1-14, which is hereby incorporated by reference in its entirety.T-Cell Modulatory Polypeptides (TMPs)The present disclosure provides T-Cell Modulatory Polypeptides (TMPs). A TMP may be capable of binding to and activating an immune cell e.g., an immune cell comprising a TCR of the present disclosure. A TMP may bind to and activate an immune cell e.g., an immune cell comprising a TCR of the present disclosure. A TMP may comprise one or more immunomodulatory polypeptides (MODs) that stimulate activation and / or proliferation of an immune cell e.g., an immune cell comprising a TCR of the present disclosure.In the present disclosure, T-Cell Modulatory Polypeptides may also be referred to as TMPs, Immuno- STATs or ISTs. These terms are used interchangeably in the present disclosure.In some cases, a T-Cell Modulatory Polypeptide (‘TMP’) comprises (i) a short polypeptide (e.g., from 4 to 20 amino acids) that comprises an epitope from a protein such as a cancer-associated protein, an autoimmune-associated protein or a pathogen-associated protein (a ‘peptide epitope’); (ii) a first major histocompatibility complex (MHC) class I polypeptide that is a beta-2 microglobulin (‘|32M’) polypeptide; (ill) a second MHC class I polypeptide that is heavy chain polypeptide; (iv) one or more immunomodulatory polypeptides (‘MODs’), e.g., one or more variant IL-2 MODs; and (v) a scaffold component such as an Ig Fc polypeptide, e.g., an lgG1 Fc polypeptide.Each TMP thus comprises a peptide-MHC complex (a ‘pMHC’) that is formed by the combination of the peptide epitope and MHC class I polypeptides. The pMHC presents an epitope that can specifically bind to a T-cell receptor (‘TCR’) of a target T cell.Each TMP may comprise one or more independently selected peptide linkers between any two adjacent components of the TMP, e.g., between one or more of: (i) the peptide epitope and the p2M polypeptide (when the peptide epitope is part of a fusion polypeptide with the 02 M polypeptide); (ii) the MHC class I heavy chain polypeptide and a MOD; (ill) the MHC class I heavy chain polypeptide and a scaffold component such as an Ig Fc polypeptide; (iv) an Ig Fc polypeptide and a MOD; and (v) where there is more than one MOD in tandem, between the MODs. As discussed below, where each TMP is a heterodimer of two polypeptides, it can contain one or more interchain disulfide bonds that link the two polypeptides, as well as one or more intrachain disulfide bonds. Where each TMP is a single-chain polypeptide, it can contain one or more intrachain disulfide bonds. As also discussed below, the peptide epitope may either be part of a fusion protein or chemically conjugated to either of the MHC class I polypeptides.When a TMP comprises an Ig Fc polypeptide, it may (and often will) form a dimeric TMP (a ‘DTMP’) by spontaneously forming one or more (typically two) disulfide bonds between one or more (typically two)cysteines in the Ig Fc polypeptide of one TMP and one or more (typically two) cysteines in the Ig Fc polypeptide of another TMP. A DTMP is thus a homodimer or heterodimer that comprises two TMPs.In some embodiments, the TMP comprises:I) a peptide epitope; ii) a first major histocompatibility complex (MHC) class I polypeptide, wherein the first MHC class I polypeptide is a p2-microglobulin ( 2M) polypeptide; ill) one or more immunomodulatory polypeptides; iv) a second MHC class I polypeptide, wherein the second MHC class I polypeptide is a MHC class I heavy chain polypeptide; and v) a scaffold polypeptide, optionally an immunoglobulin (Ig) Fc polypeptide, and wherein the TMP presents a peptide:MHC complex comprising the MHC class I heavy chain polypeptide and the peptide epitope, and . wherein the TMP may comprise one or more independently selected peptide linkers between any two of the component polypeptides, and wherein when the TMP comprises more than one immunomodulatory polypeptide, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.In some embodiments, the TMP is a dimeric TMP (a DTMP) comprising two heterodimeric TMPs described herein, and wherein one or more disulfide bonds link the Ig Fc polypeptide of one heterodimeric TMP to the Ig Fc polypeptide of the other heterodimeric TMP. In some embodiments, the DTMP is a homodimer comprising two copies of a TMP described herein. In some embodiments, the DTMP is a heterodimer comprising two different TMPs described herein.A. TMPs In Which The Peptide Epitope Is Part Of A Fusion ProteinIn some cases, a TMP is a heterodimeric polypeptide. See, e.g., Published PCT applications WO2018 / 119114, WO2020 / 132135, WO2020 / 132136, WO2020 / 132138, W02020 / 132297, andWO2021 / 231376 to Cue Biopharma, Inc., which disclose heterodimeric TMPs (referred to therein as ‘T- cell multimeric polypeptides or TMMPs’), the disclosure of which as they pertain to heterodimeric T cell modulatory proteins (TMPs), and homodimers and heterodimers comprising such TMPs, is expressly incorporated herein by reference.In some cases, TMPs are single-chain polypeptides. Examples of single-chain TMPs and DTMPs thereof, are described in WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to single-chain TMP polypeptides and DTMPs comprising two single-chain TMP polypeptides, is expressly incorporated herein by reference.In some cases, a TMP is a multimeric antigen-presenting polypeptide (MAPP) or is a dimer of a MAPP as described in WO2021 / 242935 (Cue Biopharma, Inc.) or WO2022 / 099157 (Cue Biopharma, Inc.), the disclosures of which as they pertain to MAPPs and dimers thereof, are expressly incorporated by reference.1. Heterodimeric TMPsAs noted above, in some cases the TMP is a heterodimer, or is a DTMP (a homodimer or a heterodimer) comprising two heterodimers.In some embodiments, the TMP is a heterodimer that comprises: a) a first polypeptide comprising: i) the peptide epitope; and ii) the 02-microglobulin (02M) polypeptide; and b) a second polypeptide comprising: i) the one or more immunomodulatory polypeptides; ii) the MHC class I heavy chain polypeptide; and ill) an immunoglobulin (Ig) Fc polypeptide, wherein the TMP may comprise one or more independently selected peptide linkers between any two of the component polypeptides, and wherein when the TMP comprises more than one immunomodulatory polypeptide, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.The components of the TMP can be arranged in any of a variety of configurations. See, e.g., FIGS. 1 A- 1 F, 2A-2F, 12A-12D, 13A-13C, and 14 of WO2020 / 132138 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such figures and the disclosure of configurations of heterodimeric TMPs, and homodimers and heterodimers of such heterodimeric TMPs, is expressly incorporated herein by reference.In some cases, a heterodimeric TMP comprises: (a) a first polypeptide comprising, in order from N- terminus to C-terminus: (I) a peptide epitope; (ii) a peptide linker; and (ill) a 02M polypeptide; and (b) a second polypeptide comprising, from the N-terminal to C-terminal direction: (I) one or more MODs; (ii) an MHC class I heavy chain polypeptide; and (ill) an Ig Fc polypeptide, i.e., the MOD(s) is / are at the N- terminus of the second polypeptide. Alternatively, the second polypeptide may comprise, from the N- terminal to C-terminal direction: (I) an MHC class I heavy chain polypeptide; (ii) an Ig Fc polypeptide, and (ill) one or more MODs, i.e., the MOD(s) is / are at the C-terminus of the second polypeptide. Alternatively, the second polypeptide may comprise, from the N-terminal to C-terminal direction: (I) one or more MODs; (ii) an MHC class I heavy chain polypeptide; (ill) an Ig Fc polypeptide, and (iv) one or more MODs, i.e., the MODs are at both the N-terminus and the C-terminus of the second polypeptide. Alternatively, the second polypeptide may comprise, from the N-terminal to C-terminal direction: (I) an MHC class I heavy chain polypeptide (ii) one or more MODs; and (ill) an Ig Fc polypeptide, i.e., the one or more MODs is / are interposed between the MHC class I heavy chain polypeptide and the Ig Fc polypeptide. As noted above, independently selected peptide linkers may be interposed between any two adjacent polypeptides in the second polypeptide, and when there is more than one MOD in tandem, interposed between the MODs.In some embodiments, a) the first polypeptide of each heterodimer comprises, in order from N-terminus to C-terminus:I) the peptide epitope, wherein the peptide has a length of 8-20 amino acids; ii) a peptide linker; and ill) the 02M polypeptide;b) the second polypeptide of each heterodimer comprises, in the N-terminal to C-terminal direction: i) the first variant IL-2 polypeptide; ii) a second variant IL-2 polypeptide; ill) the MHC class I heavy chain polypeptide; and iv) the Ig Fc polypeptide, wherein each variant IL-2 polypeptide has at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is other than histidine and amino acid 42 is other than phenylalanine, and wherein the second polypeptide comprises an independently selected peptide linker between one or more of: a) the first immunomodulatory polypeptide and the second immunomodulatory polypeptide; b) the second immunomodulatory polypeptide and the MHC class I heavy chain polypeptide; and c) the MHC class I heavy chain polypeptide and the Ig Fc polypeptide.In some embodiments, a) the first polypeptide of each heterodimer comprises, in order from N-terminus to C-terminus: i) the peptide epitope, wherein the peptide has a length of 8-20 amino acids; ii) a peptide linker; and ill) the [32M polypeptide; b) the second polypeptide of each heterodimer comprises, in the N-terminal to C-terminal direction: i) the MHC class I heavy chain polypeptide; ii) the Ig Fc polypeptide; ill) the first variant IL-2 polypeptide; and iv) a second variant IL-2 polypeptide, wherein the scaffold is a variant Ig Fc polypeptide comprising one or more amino acid substitutions that reduce or substantially eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC), wherein each variant IL-2 polypeptide has at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is other than histidine and amino acid 42 is other than phenylalanine, and wherein the second polypeptide comprises an independently selected peptide linker between one or more of: a) the MHC class I heavy chain polypeptide and the Ig Fc polypeptide b) the Ig Fc polypeptide and the first immunomodulatory polypeptide; and c) the first immunomodulatory polypeptide and the second immunomodulatory polypeptide.The first and second polypeptides of each heterodimer are typically connected by at least one disulfide bond that spontaneously forms between one or more Cys residues that are substituted into the first polypeptide and one or more Cys residues that are substituted into the second polypeptide. For example, the first and second polypeptides of a heterodimer may be joined by a disulfide bond that (i) connects aCys residue substituted into the amino acid sequence of the 2M polypeptide to a Cys residue substituted into the amino acid sequence of the MHC class I heavy chain (e.g., a disulfide bond between the Cysresidue at amino acid 12 of the 02M polypeptide and the Cys residue at amino acid 236 of the MHC class I heavy chain polypeptide). A disulfide bond formed between a Cys amino acid in 02 M polypeptide and a Cys in the MHC class I heavy chain polypeptide may be referred to herein as a ‘body disulfide.’Additionally, or alternatively, the first and second polypeptides of a heterodimer may be joined by a disulfide bond that connects (i) a Cys residue in the linker that joins the peptide epitope and the 02M polypeptide to (ii) a Cys residue substituted in the a1 or a2 subunit of the MHC class I heavy chain polypeptide. A disulfide bond formed between (I) a Cys amino acid in the linker between a peptide epitope and a 02M polypeptide and (ii) a Cys in the MHC class I heavy chain polypeptide may be referred to as a 'linker disulfide.’A heterodimeric or single-chain TMP may comprise either or both of a linker disulfide and a body disulfide. For example, the first and second polypeptides of a heterodimer may be joined by a first disulfide bond (a body disulfide) that connects a Cys residue in the 02M polypeptide to a Cys residue in the MHC class I heavy chain (e.g., a disulfide bond between the Cys residue at amino acid 12 of the 02M polypeptide and the Cys residue at amino acid 236 of the MHC class I heavy chain polypeptide), and a second disulfide bond (a linker disulfide) that connects (I) a Cys residue in the linker (e.g., a G2C linker as discussed below) that joins the peptide epitope to the 02M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide, e.g., a Cys substituted for Y84 in the a1 subunit or for a Cys substituted at any one of amino acids 135-143 (e.g., at position A139) in the a2 subunit of the MHC heavy chain polypeptide.Two identical heterodimeric TMPs may join to form a homodimeric DTMP by the spontaneous formation of one or more disulfide bonds (typically two disulfide bonds) that join one or more (typically two) cysteines in the Ig Fc polypeptide of one heterodimeric TMP to one or more (typically two) cysteines in the Ig Fc polypeptide of the other heterodimeric TMP. Alternatively, where a DTMP of two different heterodimeric TMPs is desired, the Ig Fc polypeptides of the two heterodimers may comprise interspecific binding sequences (e.g., ‘Knob-in-Hole’ sequences) that permit two different TMPs to selectively dimerize. Interspecific binding sequences favor formation of heterodimers with their cognate polypeptide sequence (i.e., the interspecific sequence and its counterpart interspecific sequence), particularly those based on Ig Fc sequence variants. Such interspecific sequences are well known. See, e.g., PCT application WO2022 / 197970 (Cue Biopharma, Inc.) at paragraph

[0210] , which discloses examples of such interspecific binding sequences, the disclosure of which is expressly incorporated herein by reference.2. Single-chain TMPSAs noted above, in some cases, a TMP is a single-chain polypeptide. The components of the single-chain TMP can be arranged in any of a variety of configurations. See, e.g., FIGS. 12 and 13 and the disclosure of WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such figures and the disclosure of configurations of single-chain TMPs, and homodimers and heterodimers of such singlechain TMPs, is expressly incorporated herein by reference.A single-chain TMP comprises, from the N-terminal to C-terminal direction: (I) a peptide epitope; (ii) a peptide linker; (Hi) a 02M polypeptide; (iv) an optional peptide linker; (v) an MHC class I heavy chainpolypeptide; (vi) an optional peptide linker; (vii) an Ig Fc polypeptide; (viii) an optional peptide linker; and (lx) one or more MODs. Alternatively, the one or more MODs may be interposed between the MHC class I heavy chain polypeptide and Ig Fc polypeptide. If the TMP comprises two or more MODs in tandem, then the MODs may be separated by independently selected peptide linkers. In some cases, the TMP comprises a Cys-containing peptide linker between the peptide epitope and the 2M polypeptide, and the TMP comprises an intrachain disulfide bond (i.e., a ‘linker disulfide’) between the Cys present in the peptide linker and a Cys in the MHC class I heavy chain polypeptide, e.g., a Cys substituted for Y84 in the a1 subunit or for A139 in the a2 subunit of the MHC heavy chain polypeptide. In some cases, the single-chain TMP comprises an intrachain disulfide bond ( / .e., a ‘body disulfide’) formed between a Cys residue in the 2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide. In some cases, the single-chain TMP comprises both a linker disulfide and one or more body disulfides.B. TMPs In Which The Peptide Epitope Is Chemically ConjugatedIn the above-described TMPs, the peptide epitope is part of a fusion protein with the 2M polypeptide. In some cases, however, the peptide epitope is chemically conjugated to a stabilized MHC complex to form a pMHC. In such cases, the peptide epitope may be chemically conjugated to a chemical conjugation site in the P2M polypeptide or MHC class I heavy chain polypeptide. For example, the peptide epitope may be chemically conjugated to a chemical conjugation site (e.g., a Cys) that is provided in the 2M polypeptide. The stabilized MHC and chemically conjugated peptide thus form a pMHC that allows the TMP to selectively modulate target T cells.Heterodimeric TMP’s comprising chemically conjugated peptide epitopes, and DTMPs comprising two of such heterodimeric polypeptides, are disclosed in W02020 / 132368 (Cue Biopharma, Inc.), the disclosure of which is expressly incorporated herein by reference. Single-chain TMPs comprising chemically conjugated peptide epitopes, and DTMPs comprising two of such single-chain polypeptides are disclosed in W02022 / 015880 (Cue Biopharma, Inc.), the disclosure of which is expressly incorporated by reference. Such TMPs comprising chemically conjugated peptide epitopes may comprise one or more body disulfides but typically will not comprise a linker disulfide. Such TMPs also provide the advantage of being able to conjugate and present epitopes that are not simply peptides as in the fusion proteins described above.C. MHC Polypeptides1. P2M polypeptidesThe 2M polypeptide present in the TMPs and TMPs can comprise an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to the P2M amino acid sequence of FIG. 1A of WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to that sequence and figure is expressly incorporated herein by reference. In some cases, the 2M polypeptide comprises a Cys at position 12. In such cases, the 2M polypeptide comprises an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to the 2M amino acid sequence of FIG. 1B of WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to that sequence and figure is expressly incorporated herein by reference. In some embodiments, when the 2M polypeptide comprises a Cys at position 12, it can forma disulfide bond with a Cys substituted into the amino acid sequence of the MHC class I heavy chain polypeptide (discussed below), e.g., at position 236. In some cases, the p2M polypeptide comprises an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to SEQ ID NO:435.2. MHC class I heavy chain polypeptidesAs noted above, a TMP comprises an MHC class I heavy chain polypeptide. An ‘MHC class I heavy chain polypeptide' that is found in a human may also be referred to as a human leukocyte antigen (HLA) class I heavy chain polypeptide. In some cases, the MHC class I heavy chain is a heavy chain from an HLA-A, -B, -C, or -E allele. In some cases, the MHC class I heavy chain is a heavy chain from HLA- A*0101 , A*0201 , A*0301 , A*1101 , A*2301 , A*2402, A*2407, A*3303, and / or A*3401 . In some cases, the MHC class I heavy chain is a heavy chain from HLA- B*0702, B*0801 , B*1502, B*3802, B*4001 , B*4601 , and / or B*5301 . In some cases, the MHC class I heavy chain is a heavy chain from C*0102, C*0303, C*0304, C*0401 , C*0602, C*0701 , C*702, C*0801 , and / or C*1502. The amino acid sequences of these MHC class I heavy chain polypeptides are well known, see, e.g., FIGS. 3A-3E, 4A-4E, 5A-5E, 6A-6E, 7A- 7B, 8A-8B, and 9A-9B of WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to those sequences and figures is expressly incorporated herein by reference.In some cases, the MHC class I heavy chain is a heavy chain from HLA-E*0101 (HLA-E*01 :01 :01 :01 ), HLA-E*01 :03(HLA-E*01 :03:01 :01), HLA-E*01 :04, HLA-E*01 :05, HLA-E*01 :06, HLA-E*01 :07, HLA- E*01 :09, and HLA-E*01 :10. Two HLA-E alleles that have a significant prevalence in humans are HLA- E*01 :01 (HLA-E*01 :01 :01 :01 ) and HLA-E*01 :03(HLA-E*01 :03:01 :01 ). The amino acid sequences of these two HLA-E alleles are likewise known, and share such a high degree of sequence identity such that a TMP comprising either allele typically will not evoke an immune reaction when administered to a patient regardless of their HLA-E haplotype. See FIGS. 11A-11 D of WO2023 / 201254 (Cue Biopharma, Inc.), which provide the sequences of HLA-E*01 :01 and HLA-E*01 :03, both wild-type (FIGS. 11 A and C) and with Cys residues substituted at positions 84 and 236 (FIGS. 11 B and 11 D). See also FIG. 10 of WO2022 / 197970 (Cue Biopharma, Inc.), which provides a consensus sequence for various HLA-E alleles. The disclosure of WO2022 / 197970 as it pertains to the consensus sequence and FIG. 10, and the disclosure of the wild-type and variant sequences of FIGS 11A-11 D of WO2023 / 201254, are expressly incorporated herein by reference. Typically, when engineered immune cells such as TCR-T cells are administered to a patient, the allele of the MHC class I heavy chain of a TMP will be chosen to match an allele of the heavy chain expressed by the patient’s own cells in order to prevent an immune reaction from occurring. Such a match may not be required, however, when the engineered immune cell (e.g., TCR-T cell) comprises an exogenous TCR that binds to a target peptide:MHC complex comprising an HLA-E*01 :01 or HLA-E*01 :03 heavy chain.In some cases, the TMP comprises an MHC class I HLA-A allele heavy chain. In some cases, the MHC class I heavy chain polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to one of the HLA-A heavy chain amino acid sequences of 3A-3E, 4A-4E, 5A-5E, 6A-6E or 7A of published PCT application WO2022 / 197970 (Cue Biopharma, Inc.).In some cases, the MHC class I heavy chain polypeptide comprises an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to SEQ ID NO:436. a. Heterodimeric TMPsAs noted above, when the TMP is a heterodimer, the first polypeptide will comprise the 02M polypeptide and the peptide epitope, and the second polypeptide will comprise the MHC class I heavy chain. Such heterodimeric TMPs typically will comprise one or more interchain disulfide bonds formed between one or more Cys residues in the MHC class I heavy chain polypeptide and one or more Cys residues in the first polypeptide. Such TMPs also may comprise an intrachain disulfide bond.In some cases, the MHC class I heavy chain polypeptide of the second polypeptide may comprise a Cys at position 84 and a Cys at position 139. In such cases, an intrachain disulfide bond will be formed between the Cys at position 84 and a Cys at position 139.As noted above, in some cases a Cys is substituted at position 12 of the 2M polypeptide of the first polypeptide. In such cases, as Cys may be substituted at position 236 of the MHC class I heavy chain in the second polypeptide and an interchain disulfide bond (i.e., a body disulfide) will be formed with the Cys at position 12 of the 02M polypeptide.As also noted above, in some cases the linker connecting the 02M polypeptide and the peptide epitope comprises a Cys residue, and the MHC class I heavy chain polypeptide will comprise a Cys at position 84 in the a1 subunit or a Cys at any one of amino acids 135-143 (e.g., at position A139) in the a2 subunit. In such cases, a disulfide bond i.e., a linker disulfide) will be formed between the Cys-containing linker and the Cys at position 84 or the Cys at any one of amino acids 135-143 e.g., at position A139). When the TMP comprises such a linker disulfide, the TMP will not include the intrachain disulfide discussed above formed between the Cys at position 84 and a Cys at position 139.In some cases, a heterodimeric TMP will have both a body disulfide and a linker disulfide as mentioned above. Heterodimeric TMPs comprising both a linker disulfide and a body disulfide are disclosed, e.g., in published PCT applications WO2020 / 132135, WO2020 / 132136, WO2020 / 132138, W02020 / 132297 and WO2021 / 231376 (Cue Biopharma, Inc.), the disclosures of which as they pertain to such TMPs are expressly incorporated herein by reference.In some cases, the MHC class I heavy chain polypeptide also may include an alanine at position 84, i.e., a Y84A substitution. b. Single-chain TMPsWhen the TMP is a single-chain TMP, the TMP may comprise one or more intrachain disulfide bonds, including either or both a linker disulfide and one or more intrachain disulfides. As with the heterodimeric TMPs discussed above, a linker disulfide may be formed between: (I) a Cys present in a peptide linker interposed between the peptide epitope and the 02M polypeptide (e.g., a G2C linker), and (ii) a Cys substituted for one of the amino acids in the peptide binding groove of the MHC class I heavy chain polypeptide, e.g., a Cys substituted at position 84 or a Cys substituted at any one of amino acids 135-143(e.g., at position 139). Where such a linker disulfide is formed with a Cys substituted at any one of amino acids 135-143, e.g., at position 139, then the amino acid at position 84 is other than a Cys, e.g., is Ala, Gly, Vai or Tyr. Conversely, where such a linker disulfide is formed with a Cys substituted at position 84, then amino acids 135-143, e.g., at position 139, are other than Cys residues. Alternatively, or additionally, the single-chain TMP may comprise an intrachain disulfide bond formed between a Cys substituted at position 236 with a Cys substituted at position 12 of the 2M polypeptide discussed above.In some cases, the MHC class I heavy chain polypeptide also may include an alanine at position 84, i.e., a Y84A substitution.D. Scaffold PolypeptidesAs noted above, a TMP typically comprises a scaffold polypeptide such as an Ig Fc polypeptide. An Ig Fc polypeptide of a TMP can be a human lgG1 Fc, a human lgG2 Fc, a human lgG3 Fc, a human lgG4 Fc, etc., or a variant of a wild-type Ig Fc polypeptide. Variants include naturally occurring variants, non- naturally occurring variants, and combinations thereof. For example, the Ig Fc can be a variant of an Fc polypeptide such as a human lgG1 Fc, which variant has a reduced or substantially eliminated effector function, i.e., the ability to effect complement-dependent cytotoxicity (CDC) and / or antibody-dependent cell-mediated cytotoxicity (ADCC). Such variants are well known and described in scientific literature. See also published PCT applications WO2020 / 132135, WO2020 / 132136, WO2020 / 132138,W02020 / 132297 and WO2021 / 231376 (Cue Biopharma, Inc.), the disclosures of which as they pertain to such Ig Fc polypeptides and variants are expressly incorporated herein by reference. In some embodiments, the scaffold is a variant Ig Fc polypeptide comprising one or more amino acid substitutions that reduce or substantially eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC).In some cases, e.g., where TMP comprises a heterodimer of first and second polypeptides, the Ig Fc may be at the C-terminus of the second polypeptide. In such cases, the Ig Fc polypeptide optionally may not comprise a C-terminal Lys.In some cases, the Fc polypeptide present in a TMP is an IgG 1 Fc polypeptide, or a variant of an IgG 1 Fc polypeptide. For example, in some cases, the IgG 1 Fc polypeptide present in a TMP comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to any one of the human Ig Fc polypeptide amino acid sequences of FIGS. 5A-5H of PCT application and WO2021 / 231376 (Cue Biopharma, Inc.), the disclosure of which as it pertains to the sequences of FIGS. 5A-5H is expressly incorporated herein by reference.In some cases, the Ig Fc polypeptide present in a TMP comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to the lgG1 Fc polypeptide amino acid sequence set forth in FIGS. 5G and 5H of PCT application and WO2021 / 231376 (Cue Biopharma, Inc.), where amino acid 14 is an Ala and amino acid 15 is an Ala. Such substitutions of Ala for Leu at amino acids 14 and 15 are known as the ‘LALA’ mutations. In some cases, the scaffold polypeptide (e.g., an Ig Fc polypeptide) comprises an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to SEQ ID NO:437.E. Immunomodulatory Polypeptides (MODs)As noted above, a TMP comprises one or more immunomodulatory polypeptides (‘MODs’). In some cases, a MOD present in the TMP is a wild-type fwt’) MOD. In other cases, a MOD present in a TMP is a variant of a wt MOD that has reduced affinity for a co-MOD compared to the affinity of a corresponding wild-type MOD for the co-MOD. Suitable MODs that exhibit reduced affinity for a co-MOD can have from1 amino acid (aa) to 20 aa differences from a wild-type MOD. For example, in some cases, a variant MOD present in a TMP differs in amino acid sequence by 1 aa, 2 aa, 3 aa, 4 aa, 5 aa, 6 aa, 7 aa, 8 aa, 9 aa, or 10 aa, from a corresponding wild-type MOD. As another example, in some cases, a variant MOD present in a TMP differs in amino acid sequence by 1 1 aa, 12 aa, 13 aa, 14 aa, 15 aa, 16 aa, 17 aa, 18 aa, 19 aa, or 20 aa, from a corresponding wild-type MOD.TMPs used in combination with engineered immune cells of this disclosure (e.g., TCR-T cells) will usually comprise ‘activating’ MODs, i.e., MODs that promote / stimulate activation and / or proliferation of the immune cell (e.g., T cell) to which the TMP binds. Activating MODs, which can be either a wild-type MOD or a variant MOD, include but are not limited to IL-2, IL-7, IL-12, IL-15, IL-17, IL-21 , IL-27, IL-23, CD28, CD80, CD86, 4-1 BBL, OX40L, CD70, ICOS-L, CD40, ICAM (CD54), GITRL, and TGF . Wild-type and variant MODs, including reduced affinity variants, such as CD80, CD86, 4-1 BBL and IL-2 are described in the published literature, e.g., published PCT application WO2019 / 051091 , WO2020 / 132138 and WO2023 / 097188 (Cue Biopharma, Inc.), the disclosures of which as they pertain to MODs and specific variant MODs, e.g., of CD80, CD86, 4-1 BBL, and IL-2 are expressly incorporated herein by reference. In some embodiments, at least one of the one or more immunomodulatory polypeptides is an activating polypeptide. In some embodiments, the activating polypeptide is a wild type or variant polypeptide selected from a 4-1 BBL polypeptide, a CD80 polypeptide, a CD86 polypeptide, an IL-2 polypeptide, an IL- 7 polypeptide, an IL-12 polypeptide, an IL-15 polypeptide, an IL-21 polypeptide, an ICOS polypeptide, an 0x40 polypeptide or a CD40 polypeptide.In some cases, a TMP comprises more than one copy of an activating MOD. Where a TMP comprises two or more copies of an activating MOD in tandem, a peptide linker may be interposed between the copies.In some cases, a TMP comprises at least one MOD that is a variant of the cytokine IL-2. Wild-type IL-2 binds to IL-2 receptor (IL-2R) on the surface of a T cell. Wild-type IL-2 has a strong affinity for IL-2R and will bind to activate most or substantially all CD8+ T cells. For this reason, synthetic forms of wild type IL-2 such as the drug Aldesleukin (trade name Proleukin®) are known to have severe side-effects when administered to humans for the treatment of cancer because the IL-2 indiscriminately activates both target and non-target T cells.As disclosed in the above cited published PCT applications, e.g., WO2023 / 097188 to Cue Biopharma, Inc., an IL-2 receptor is a heterotrimeric polypeptide comprising an alpha chain (IL-2Ra; also referred to as CD25), a beta chain (IL-2R|3; also referred to as CD122: and a gamma chain (IL-2Ry; also referred to as CD132). A wild-type IL-2 polypeptide can have the following amino acid sequence:APTSSSTKKT QLQLEHLLLD LQMILNGINN YKNPKLTRML TFKFYMPKKA TELKHLQCLE EELKPLEEVL NLAQSKNFHL RPRDLISNIN VIVLELKGSE TTFMCEYADE TATIVEFLNRWITFCQSIIS TLT (SEQ ID NO:375)In some cases, an IL-2 variant MOD of this disclosure exhibits decreased binding to IL-2Ra, thereby minimizing or substantially reducing the activation of regulatory T cells (‘Tregs’) by the IL-2 variant. Alternatively, or additionally, in some cases, an IL-2 variant MOD of this disclosure exhibits decreased binding to IL-2R0 and / or IL-2Ry such that the IL-2 variant MOD exhibits an overall reduced affinity for IL- 2R. In some cases, an IL-2 variant MOD of this disclosure exhibits both properties, i.e., it exhibits decreased or substantially no binding to IL-2Ra, and also exhibits decreased binding to IL-2R and / or IL- 2Ry such that the IL-2 variant polypeptide exhibits an overall reduced affinity for IL-2R. See, e.g., paragraphs

[0167] to

[0201] of published PCT application WO2023 / 097188, the disclosure of which as it pertains to variant IL-2 MODs that have reduced binding to IL-2Ra and / or IL-2R , is expressly incorporated herein by reference.In some cases, an IL-2 variant MOD of this disclosure exhibits decreased or substantially no binding to IL- 2Ra, and also exhibits decreased binding to IL-2R such that the IL-2 variant polypeptide exhibits an overall reduced affinity for IL-2R. Exemplary combinations of mutations that reduce binding of an IL-2 variant polypeptide to IL-2Ra and IL-2R are provided in Table 5 of WO2023 / 097188 (Cue Biopharma, Inc.), the disclosure of which as it pertains to Table 5 is expressly incorporated herein by reference.For example, IL-2 variants having substitutions at H16 and F42 have shown decreased binding to IL-2Ra and IL-2R . See, Quayle et al., Clin Cancer Res; 26(8) April 15, 2020, which discloses that the binding affinity of an IL-2 polypeptide with H16A and F42 A substitutions for human IL-2Ra and IL-2R was decreased 110- and 3-fold, respectively, compared with wild-type IL-2 binding, predominantly due to a faster off-rate for each of these interactions. TMPs comprising such IL-2 variants that exhibit decreased binding to IL-2Ra and IL-2R , have shown the ability to preferentially bind to and activate IL-2 receptors on T cells that contain the target TCR that is specific for the epitope presented by the pMHC of the TMP, and are thus less likely to deliver IL-2 to non-target T cells, i.e., T cells that do not contain a TCR that specifically binds the epitope presented by the pMHC of the TMP. In such cases, the binding of the IL-2 variant MOD to its costimulatory polypeptide on the T cell is substantially driven by the binding of the MHC-epitope moiety rather than by the binding of the variant IL-2 polypeptide to IL-2R receptors on the T cell.Suitable IL-2 variant MODs thus include a polypeptide that comprises an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98%, or at least 99% amino acid sequence identity to the wt IL-2 amino acid sequence (SEQ ID NO:375) and that have one or more amino acid differences from the wt IL-2 amino acid sequence. In some cases, such a variant IL-2 polypeptide of this disclosure exhibits reduced binding affinity to IL-2R, compared to the binding affinity of wt IL-2 (SEQ ID NO:375). For example, in some cases, a variant IL-2 polypeptide binds IL-2R with a binding affinity that is at least 10% less, at least 15% less, at least 20% less, at least 25%, at least 30% less, at least 35% less, at least 40% less, at least 45% less, at least 50% less, at least 55% less, at least 60% less, at least 65% less, at least 70% less, at least 75% less, at least 80% less, at least 85% less, at least 90% less, at least 95%less, or more than 95% less, than the binding affinity of wt IL-2 for IL-2R when assayed under the same conditions.In some cases, a suitable variant IL-2 polypeptide comprises an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or 100% amino acid sequence identity to the following amino acid sequence where amino acid 16 (denoted by Xi) is other than His, and where amino acid 42 (denoted by X2) is other than Phe:APTSSSTKKT QLQLEXiLLLD LQMILNGINN YKNPKLTRML TX2KFYMPKKA TELKHLQCLE EELKPLEEVL NLAQSKNFHL RPRDLISNIN VIVLELKGSE TTFMCEYADE TATIVEFLNRWITFCQSIIS TLT (SEQ ID NO:376)As noted above, such IL-2 variant polypeptides exhibit an overall reduced affinity for IL-2R as compared to the affinity of wild-type IL-2 for IL-2R. In some cases, Amino acid 16 is Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, lie, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Vai; and amino acid 42 is Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, His, lie, Leu, Lys, Met, Pro, Ser, Thr, Trp, Tyr, or Vai. In some cases, Amino acid 16 is Ala and amino acid 42 is Ala. In some cases, amino acid 16 is Thr and amino acid 42 is Ala. In some cases, amino acid 16 is Asp and amino acid 42 is Ala. In some cases, amino acid 16 is Glu and amino acid 16 is Ala. In some cases, a TMP comprises more than one copy of such a MOD. For example, in some cases a TMP comprises two copies of such a MOD in tandem. In such cases, the copies may be connected by a peptide linker. In some cases, a suitable variant IL-2 polypeptide comprises an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or 100% amino acid sequence identity to the following amino acid sequence where amino acids 16 and 42 are Ala:APTSSSTKKT QLQLEALLLD LQMILNGINN YKNPKLTRML TAKFYMPKKA TELKHLQCLE EELKPLEEVL NLAQSKNFHL RPRDLISNIN VIVLELKGSE TTFMCEYADE TATIVEFLNRWITFCQSIIS TLT (SEQ ID NO:377)In some cases, the MOD comprises an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or 100% amino acid sequence identity to SEQ ID NO:375, 376 or 377. In some cases, the MOD comprises an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or 100% amino acid sequence identity to SEQ ID NO:377.In some cases, a TMP comprises two copies of such a MOD in tandem. In such cases, the copies may be connected by a peptide linker. In some embodiments, the TMP comprises two variant IL-2 polypeptides in tandem, wherein the two variant IL-2 polypeptides have the same amino acid sequence, and optionally are connected by a linker.F. LinkersAs noted above, TMPs of this disclosure can include one or more independently selected polypeptide linkers (referred to as peptide linkers herein) interposed between any two polypeptide components of the TMP. Such peptide linkers are well known. See, e.g., WQ2020 / 132136 (Cue Biopharma, Inc.). For example, one or more linkers may be interposed between one or more of: I) a peptide epitope and a 2M polypeptide; ii) an MHC class I heavy chain polypeptide and an Ig Fc polypeptide; ill) an MHC class Iheavy chain polypeptide and an immunomodulatory polypeptide; iv) an Ig Fc polypeptide and an immunomodulatory polypeptide; and v) where a TMP comprises more than one immunomodulatory polypeptide in tandem, between the immunomodulatory polypeptides. In some cases, a peptide linker comprises the amino acid sequence SEQ ID NO:438, 439, or 440 (or a variant thereof in which 1 , 2, 3, 4, or 5 amino acids are substituted with another amino acid).Linkers may be a flexible peptide linker, including a short flexible peptide linker, or a rigid peptide linker. Such linkers are disclosed in WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such peptides is expressly incorporated herein by reference, including specifically, but not limited to, paragraphs

[0188] -

[0196] .As noted above, the linker between a peptide epitope and a 02M polypeptide may comprise a single Cys residue that can form a disulfide bond with a Cys in the MHC class I heavy chain polypeptide. Such Cys- containing linkers are disclosed in WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such peptide linkers is expressly incorporated herein by reference, including specifically, but not limited to, paragraphs

[0202] -

[0207] . Where the TMP comprises a heterodimer, the Cys in the linker can form a disulfide bond with a Cys in the MHC class I heavy chain polypeptide in the second polypeptide, e.g., with a Cys at position 84 or a Cys at one of positions 135-143, e.g., at position 139. Similarly, where the TMP comprises a single-chain polypeptide, the Cys in the linker can form an intrachain disulfide bond with a Cys in the MHC class I heavy chain polypeptide, e.g., with a Cys at position 84 or a Cys at one of positions 135-143, e.g., at position 139. In some cases, the linker between a peptide epitope and a 2M polypeptide comprises an amino acid sequence SEQ ID NO:438 (or a variant thereof in which 1 , 2, 3, 4, or 5 amino acids are substituted with another amino acid).G. Exemplary TMPs and DTMPsThe following TMPs and DTMPs are illustrative of TMPs and DTMPs that may be used in accordance with this disclosure.TMPs that modulate WT1 -specific T cellsNovel TMPs and DTMPs have been disclosed for selectively modulating T cells that can bind to and kill Wilms Tumor-1 -associated cancer cells. See, e.g., Published PCT applications WQ2020 / 132297, WQ2020 / 136366 and WO2021 / 231376 to Cue Biopharma, Inc. and WQ2021 / 230638 to LG Chem, Ltd., which disclose heterodimeric T cell modulatory proteins (TMPs), and DTMPs comprising such TMPs. See also PCT application WO2022 / 197970 (Cue Biopharma, Inc.), which discloses single-chain TMPs and DTMPs comprising such TMPs.Such novel DTMPs include CUE-102, which is a homodimer comprised of two identical heterodimers. Each heterodimer comprises a peptide-human leukocyte antigen (HLA) complex containing a polypeptide from a Wilms Tumor-1 (WT1 ) protein, two reduced-affinity, variant human interleukin-2 (IL-2) polypeptides, and a variant immunoglobulin G1 (IgG 1 ) Fc domain comprising amino acid substitutions that substantially eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complementdependent cytotoxicity (CDC). CUE-102 is designed to selectively activate tumor antigen-specific T cells to eradicate WT1 positive (WT1+) cancers. The heterodimers are linked together by two disulfide bondsthat join two cysteine residues in the lgG1 Fc polypeptide of one heterodimer to two cysteine residues in the IgG 1 Fc polypeptide of the other heterodimer.As noted above, CUE-102 is a homodimer comprised of two identical heterodimers. Its structure and sequence is provided in WO2021 / 231376 (Cue Biopharma, Inc.). The first polypeptide of each heterodimer in CUE-102 comprises, in order from N-terminus to C-terminus: (i) a WT1 peptide epitope comprising the amino acid sequence VLDFAPPGA (SEQ ID NOU ); (ii) a linker comprising a Cys residue, and (iii) a |32-microglobulin (02M) polypeptide. The second polypeptide comprises two variant IL-2 polypeptides, a class I MHC heavy chain polypeptide, a variant lgG1 Fc polypeptide, and peptide linkers interposed between each of the polypeptides. The sequence of the first polypeptide is provided in SEQ ID NO:422 and sequence of the second polypeptide is provided as SEQ ID NO:423. In some embodiments, the TMP comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:422, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:423. The first polypeptide and the second polypeptide of each heterodimer in CUE-102 are covalently linked to one another via a disulfide bond between a Cys residue at amino acid 12 of the 2M polypeptide and a Cys residue at amino acid 236 of the class I MHC heavy chain polypeptide. The first and second polypeptide also are covalently linked to one another via a second disulfide bond that joins (I) a Cys residue in the linker between the 02M polypeptide and the WT1 peptide to (ii) a Cys in the class I MHC heavy chain polypeptide at amino acid 84. The two heterodimers are then joined to each other by two disulfide bonds that join cysteines in the lgG1 Fc polypeptide of one heterodimer to cysteines in the lgG1 Fc polypeptide of the other heterodimer. The disclosure of WQ2021 / 231376 as it pertains to the sequences of FIGS. 14A and 14B and the TMP and DTMP comprising them is expressly incorporated herein by reference.Examples of possible WT1 peptide epitopes are described in Published PCT applications WQ2020 / 132297 and WO2021 / 231376 to Cue Biopharma, Inc. (see, e.g., paragraphs

[0264] -

[0270] of WO2021 / 231376) and WQ2021 / 230638 to LG Chem, Ltd. (see, e.g., paragraphs

[0172] -

[0177] , the disclosures of which as they pertain to such WT1 epitopes are expressly incorporated by reference.Examples of WT-1 peptide epitopes suitable for inclusion in a TMP or DTMP include, but are not limited to, CMTWNQMNLGATLKG (SEQ ID NO:378), WNQMNLGATLKGVAA (SEQ ID NO:379), CMTWNYMNLGATLKG (SEQ ID NQ:380), WNYMNLGATLKGVAA (SEQ ID NO:381 ), MTWNQMNLGATLKGV (SEQ ID NO:382), TWNQMNLGATLKGVA (SEQ ID NO:383), CMTWNLMNLGATLKG (SEQ ID NO:384), MTWNLMNLGATLKGV (SEQ ID NO:385), TWNLMNLGATLKGVA (SEQ ID NO:386), WNLMNLGATLKGVAA (SEQ ID NO:387), MNLGATLK (SEQ ID NO:388), MTWNYMNLGATLKGV (SEQ ID NO:389), TWNYMNLGATLKGVA (SEQ ID NQ:390), CMTWNQMNLGATLKGVA (SEQ ID NO:391), CMTWNLMNLGATLKGVA (SEQ ID NO:392), CMTWNYMNLGATLKGVA (SEQ ID NO:393), GYLRNPTAC (SEQ ID NO:394), GALRNPTAL (SEQ ID NO:395), YALRNPTAC (SEQ ID NO:396), GLLRNPTAC (SEQ ID NO:397), RYRPHPGAL (SEQ ID NO:398), YQRPHPGAL (SEQ ID NO:399), RLRPHPGAL (SEQ ID NQ:400), RIRPHPGAL (SEQ ID NQ:401 ), QFPNHSFKHEDPMGQ (SEQ ID NQ:402), HSFKHEDPY (SEQ ID NQ:403), QFPNHSFKHEDPM (SEQ ID NQ:404), QFPNHSFKHEDPY (SEQ ID NQ:405), KRPFMCAYPGCNK (SEQ ID NQ:406), KRPFMCAYPGCYK (SEQ ID NQ:407), FMCAYPGCY (SEQ ID NQ:408), FMCAYPGCK (SEQ ID NQ:409), KRPFMCAYPGCNKRY (SEQ ID NQ:410), SEKRPFMCAYPGCNK(SEQ ID N0:411 ), KRPFMCAYPGCYKRY (SEQ ID NO:412), NLMNLGATL (SEQ ID NO:413), VLDFAPPGA (SEQ ID N0:1); RMFPNAPYL (SEQ ID NO:414); CMTWNQMN (SEQ ID NO:415); CYTWNQMNL (SEQ ID NO:416); NYMNLGATL (SEQ ID NO:417); YMFPNAPYL (SEQ ID NO:418); SLGEQQYSV (SEQ ID NO:419); CMTWNQMNL (SEQ ID NQ:420); and NQMNLGATL (SEQ ID NO:421). In some cases, the WT-1 peptide present in a TMP is CMTWNQMN (SEQ ID NO:415) In some cases, the WT-1 peptide present in a TMP is CYTWNQMNL (SEQ ID NO:416).In some cases, the WT-1 peptide present in a TMP presents an HLA-A*24:02-restricted epitope. WT-1 peptides that present an HLA-A*24:02-restricted epitope include, e.g., CMTWNQMN (SEQ ID NO:415); NYMNLGATL (SEQ ID NO:417) (WT-1 239-247; Q240Y); CYTWNQMNL (SEQ ID NO:416) (WT-1 235- 243); CMTWNQMNL (SEQ ID NQ:420) (WT-1 235-243); NQMNLGATL (SEQ ID NO:421 ) (WT-1 239- 247); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L).In some cases, the WT-1 peptide present in a TMP presents an HLA-A*02:01 -restricted epitope. WT-1 peptides that present an HLA-A*02:01 -restricted epitope include, e.g., VLDFAPPGA (SEQ ID NO:1 ) (WT- 1 37-45); RMFPNAPYL (SEQ ID NO:414) (WT-1 126-134); YMFPNAPYL (SEQ ID NO:418) (WT-1 126- 134; R126Y); SLGEQQYSV (SEQ ID NO:419) (WT-1 187-195); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L).In some cases, a WT-1 peptide present in a TMP presents an HLA-A*24.02-restricted epitope and does not have an N-terminal Cys. For example, where a WT-1 peptide comprises an N-terminal Cys, the N- terminal Cys can be replaced by a Ser. As another example, where a WT-1 peptide comprises an N- terminal Cys, a Gly can be added to the N-terminus. For example, a WT-1 peptide present in a TMP can comprise the amino acid sequence X1X2X3TWNQMNL (SEQ ID NO:424) or X2X3TWNQMNL (SEQ ID NO:425), where each of X1 , X2, and X3 is independently any amino acid, with the proviso that the N- terminal amino acid is not a Cys, and where the WT-1 peptide epitope has a length from 9 to 25 amino acids. In some of these embodiments, the WT-1 peptide has a length of 9 amino acids or 10 amino acids. Examples of WT-1 peptides suitable for inclusion in a TMP include, but are not limited to, SMTWNQMNL (SEQ ID NO:426), GCMTWNQMNL (SEQ ID NO:427), SYTWNQMNL (SEQ ID NO:428), or GCYTWNQMNL (SEQ ID NO:429).In some cases, the WT1 (126-134;M127Y) peptide RYFPNAPYL (SEQ ID NO:373) is used with a TMP having a class I MHC heavy chain that is associated with HLA-A24:01 . In some cases, the peptides 302- 310 (RVPGVAPTL) (SEQ ID NQ:430), 302-310;V303Y (RYPGVAPTL) (SEQ ID NO:431 ), and 417- 425;W418Y (RYPSCQKKF) (SEQ ID NO:432), may be used with a TMP having a class I MHC heavy chain that is associated with HLA-A24:01 .A WT 1 peptide can have a length of at least 4 amino acids, e.g., from 4-20 aa (e.g., 4 amino acids (aa), 5 aa, 6 aa, 7 aa, 8 aa, 9 aa, 10 aa, 11 aa, 12 aa, 13 aa, 14 aa, 15 aa, 16 aa, 17 aa, 18 aa, 19 aa or 20 aa), including a range of from 6-15 aa, 8-12 aa, 8-14 aa, 8-16 aa, 8-10 aa, 9-11 aa, 5-10 aa, 10-15 aa, and 15-20 aa in length. In some cases, the peptide is 8, 9, 10, 11 , 12, 13, 14, 15 or 16 amino acids in length.TMPs that modulate AFP-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for alpha fetoprotein (AFP). See, e.g., See PCT applications WO2022 / 197970, WO2020 / 132135 and W02020 / 132365 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate MUC1 -specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for mucin-1 (MUC1 ). See PCT application WO2022 / 197970 and PCT application WO2020 / 132135 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate KRAS-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for KRAS proteins comprising a cancer-associated mutation. See PCT applications WO2021 / 055594, WO2022 / 197971 , and WO2022 / 099156 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate NY-ESO-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for NY-ESO proteins (e.g., NY-ESO-1 or NY-ESO-2) associated with various cancers. See PCT applications WO2022 / 197970 and WO2023 / 137158 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate MAGE-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for melanoma- associated antigen (MAGE) proteins associated with various cancers. See PCT applications WO2022 / 197970 and WO2023 / 137158 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.Examples of MAGE-A1 peptide epitopes suitable for inclusion in a TMP or DTMP include, but are not limited to, peptides comprising or consisting of the amino acid sequence of SEQ ID NO:191 or 223. In some cases, the MAGE-A1 peptide present in a TMP presents an HLA-A*02-restricted epitope (e.g., an HLA-A*02:01 -restricted epitope). MAGE-A1 peptides that present an HLA-A*02:01 -restricted epitope (e.g., an HLA-A*02:01 -restricted epitope) include, e.g., peptides comprising or consisting of the amino acid sequence of SEQ ID NO:191 or 223.Examples of MAGE-A10 peptide epitopes suitable for inclusion in a TMP or DTMP include, but are not limited to, peptides comprising or consisting of the amino acid sequence of SEQ ID NO:225, 226, 227, or 228. In some cases, the MAGE-A10 peptide present in a TMP presents an HLA-A*02-restricted epitope (e.g., an HLA-A*02:01 -restricted epitope). MAGE-A10 peptides that present an HLA-A*02:01 -restricted epitope (e.g., an HLA-A*02:01 -restricted epitope) include, e.g., peptides comprising or consisting of the amino acid sequence of SEQ ID NO:225 or 226. In some cases, the MAGE-A10 peptide present in a TMP presents an HLA-A*24-restricted epitope (e.g., an HLA-A*24:02-restricted epitope). MAGE-A10 peptides that present an HLA-A*24:02-restricted epitope (e.g., an HLA-A*24:02-restricted epitope) include, e.g., peptides comprising or consisting of the amino acid sequence of SEQ ID NO:227 or 228.Examples of MAGE-A4 peptide epitopes suitable for inclusion in a TMP or DTMP include, but are not limited to, peptides comprising or consisting of the amino acid sequence of SEQ ID NO:433.TMPs that modulate survivin-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for survivin proteins associated with various cancers. See PCT application WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate mesothelin-specific T cellsTMPs and DTMPs have been disclosed for selectively modulating T cells specific for mesothelin proteins associated with various cancers. See PCT application WO2022 / 197970 (Cue Biopharma, Inc.), the disclosure of which as it pertains to such TMPs and DTMPs is expressly incorporated herein by reference.TMPs that modulate PRAME-specific T cellsExamples of PRAME peptide epitopes suitable for inclusion in a TMP or DTMP include, but are not limited to, peptides comprising or consisting of the amino acid sequence of SEQ ID NO:434.H. Alternative Forms of TMPsIn some cases, a TMP is a multifunctional protein (e.g., a bispecific or trispecific protein) that does not comprise a peptide:MHC complex as in the TMPs described above. In such cases, the protein comprises (i) a component that binds to the immune cell (e.g., TCR-T cell) comprising an exogenous TCR and (ii) a component that provides immunomodulation. For example, in some cases the TMP may comprise (i) an antibody or antibody fragment that specifically or non-specifically binds to the immune cell comprising the exogenous TCR, and (ii) at least one activating immunomodulatory polypeptide (MOD) such as those described above. Examples of such antibodies or fragments thereof include antibodies that (i) bind nonspecifically to CD8+ T cells, e.g., an antibody or antibody fragment that binds to CD8 or CD3, or (ii) bind specifically to the exogenous TCR or some other antigen that is specific to the immune cell, e.g., an antibody that binds specifically to the exogenous TCR or to another exogenous antigen provided on the immune cell, e.g., through introduction of an exogenous nucleic acid into the immune cell.I. TMPs That Comprise a Targeting ComponentIn some cases, a TMP as described above may further comprise a targeting component that targets the TMP to a target tissue or cell, e.g., a cancerous tissue or cancerous cell, and / or targets an immune celkTMP complex (in the case of a complex formed by the binding of a TMP to an immune cell comprising the exogenous TCR) to a particular tissue or cell, e.g., a cancerous tissue or cancerous cell. In some cases, a targeting component is an antibody or fragment that targets a cancer antigen, and such antibodies are well known. In some cases, the antibody or fragment targets a tissue or cell.Antiqens / EpitopesA cell according to the present disclosure may comprise a T cell receptor (TCR), e.g., a TCR capable of binding to an antigen. A cell according to the present disclosure may comprise a T cell receptor (TCR) capable of binding to an antigen-derived peptide. A cell according to the present disclosure may comprise a T cell receptor (TCR) capable of binding to an antigen-derived peptide, such as when presented by a major histocompatibility complex (MHC) molecule. A cell according to the present disclosure may comprise a T cell receptor (TCR), e.g., a TCR capable of binding to an epitope. A cell according to the present disclosure may comprise a T cell receptor (TCR), e.g., a TCR capable of binding to an epitope complexed with a major histocompatibility complex (MHC) molecule.An antigen-binding molecule, e.g., a TCR, according to the present disclosure may be capable of binding to an antigen. An antigen-binding molecule, e.g., a TCR, according to the present disclosure may be capable of binding to an antigen-derived peptide. An antigen-binding molecule, e.g., a TCR, according to the present disclosure may be capable of binding to an antigen-derived peptide, such as when presented by a major histocompatibility complex (MHC) molecule. An antigen-binding molecule, e.g., a TCR, according to the present disclosure may be capable of binding to an epitope. An antigen-binding molecule, e.g., a TCR, according to the present disclosure may be capable of binding to an epitope complexed with a major histocompatibility complex (MHC) molecule.As noted above, a TMP according to the present disclosure, may comprise an epitope / peptide epitope.An ‘antigen’ refers to any molecule, e.g., a peptide, that provokes an immune response or is capable of being bound by a TCR. An ‘epitope’ or ‘peptide epitope’ as used herein, refers to a portion of a polypeptide that provokes an immune response or, when presented as part of a peptide:MHC complex is capable of being bound by a TCR. The immune response may involve either antibody production, or the activation of specific immunologically competent cells, or both. A person of skill in the art would readily understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. An antigen and / or epitope can be endogenously expressed, i.e., expressed by genomic DNA, or can be recombinantly expressed. An antigen and / or epitope can be of exogenous origin. If of polypeptide origin, an antigen and / or epitope can possess modifications to the amino acids comprising the antigen and / or epitope (e.g., phosphorylation, glycosylation, cysteinylation, deamidation, and / or other post-translational modifications to the amino acids within the antigen and / or epitope). An antigen and / or epitope can be specific to a certain tissue or cell, such as a cancer cell, or it can be broadly expressed. In addition, fragments of larger molecules can act as antigens. In some embodiments herein, antigens are tumor antigens. An epitope can be present in a longer polypeptide (e.g., in a protein), or an epitope can be present as a fragment of a longer polypeptide.In some embodiments, an epitope is complexed with a major histocompatibility complex (MHC; also referred to herein as a HLA molecule, e.g., a HLA class I or class II molecule).TCRs bind, via their CDR loops, to peptides presented by molecules of the major histocompatibility complex (MHC). This TCR-MHC interaction is crucially important in cell mediated immunity, with thespecificity in the cellular immune response being attributable to MHC polymorphism, an extensive TCR repertoire, and a variable peptide cargo. The conventional T-cell response is mediated by TCR recognition of short peptide fragments bound to MHC class I or MHC class II molecules. Generally, MHC- I present peptides derived from endogenous proteins that are recognized by cytotoxic T-cells, whereas MHC-II present exogenously-derived peptides to T helper cells (see e.g., Bhati et al., Protein Science, 23:260-272 (2014), which is hereby incorporated by reference in its entirety).The term ‘HLA,’ as used herein, refers to the human leukocyte antigen. In humans, MHCs are encoded by the human leukocyte antigen (HLA) locus on chromosome 6. There are three major HLA gene loci (HLA-A, HLA-B and HLA-C) and three minor loci (HLA-E, HLA-F and HLA-G). This locus is highly polymorphic, spans over 5 mega bases and covers over 200 genes. Individual subjects normally express 6 different classical MHC-I and 6 MHC-II molecules that can differ from each other by a single amino acid, or by more than 30 amino acids. These polymorphisms mostly affect the MHC binding cleft, and thus dictate the diversity of peptides presented by each MHC molecule (Bhati et al., Protein Science, 23:260- 272 (2014)). The frequency distribution of most common HLA alleles is publicly available (http: / / www.allelefrequencies.net / top10dist.asp).MHC proteins are expressed on the surface of cells and are involved in activation of the immune response. HLA class I genes encode MHC class I molecules, which are expressed on the surface of cells in complex with peptide fragments (antigens) of self or non-self proteins. T cells expressing TCR and CD3 recognize the antigemMHC class I complex and initiate an immune response to target and destroy antigen presenting cells displaying non-self proteins.As used herein, an ‘HLA class I molecule’ or ‘MHC class I molecule’ refers to a protein product of a wildtype or variant HLA class I gene encoding an MHC class I molecule. Accordingly, ‘HLA class I molecule’ and ‘MHC class I molecule’ are used interchangeably herein.MHC class I a-chains are polymorphic, and different a-chains are capable of binding and presenting different peptides. Genes encoding MHC class I a polypeptides are highly variable, with the result that cells from different subjects often express different MHC class I molecules.The MHC Class I molecule comprises two protein chains: the alpha chain (a-chain) and the 02- microglobulin ( 2m) chain. Human 02m is encoded by the B2M gene. The amino acid sequence of 02m is set forth in SEQ ID NO: 183. The alpha chain of the MHC Class I molecule is encoded by the HLA gene complex. The HLA complex is located within the 6p21 .3 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. The HLA genes are highly variant, with over 36,000 HLA alleles and related alleles, including over 25,000 HLA Class I alleles, known in the art, encoding thousands of HLA proteins, including over 14,000 HLA Class I proteins (see, e.g., hla.alleles.org). There are at least three genes in the HLA complex that encode an MHC Class I alpha chain protein: HLA-A, HLA-B, and HLA-C. In addition, HLA-E, HLA-F, and HLA-G encode proteins that associate with 02M chain to form the MHC Class I molecule.The term ‘antigen-presenting cell’, as used herein, designates cells having the capability to present processed antigenic moiety fragments via MHC class I or MHC class II molecules. Most cell types including cancer cells can express MHC class I molecules and present fragments via MHC class I molecules, while MHC class II molecules are expressed on professional antigen presenting cells. Professional antigen-presenting cells may be a B-cell, a monocyte, or a dendritic cell. The antigen presenting cells may be synthetic, or be isolated from peripheral blood mononuclear cells (PBMCs). Artificial APCs are a type of cell line that expresses a HLA molecule of interest for testing of TCR binding. The HLA protein can be endogenously expressed, or the artificial APCs can be engineered to express the HLA molecule of interest. Artificial APCs expressing the HLA allele of interest can be loaded with peptides such that the binding of a TCR to a peptide:HLA class I complex can be tested.‘Antigen-derived’, for example ‘WT-1 -derived’, refers to an immunogenic peptide / epitope being a portion of the antigen / polypeptide (e.g., WT-1 ) from which it has been processed. For example, an antigen is processed in the cell by the proteasome or immunoproteasome and the resulting antigen-derived peptides are presented on the MHC class I or MHC class II complex.In some embodiments, the antigen is pathologically implicated. In some embodiments, a target antigen is a disease-associated antigen. A ‘disease-associated antigen’ refers to an antigen whose presence is indicative of a given disease / disease state, or an antigen for which an elevated level of the antigen is positively-correlated with a given disease / disease state. The disease-associated antigen may be an antigen whose expression is associated with the development, progression or severity of symptoms of a given disease. The disease-associated antigen may be associated with the cause or pathology of the disease, or may be expressed abnormally as a consequence of the disease. A disease-associated antigen may be an antigen of an infectious agent or pathogen, a cancer-associated antigen or an autoimmune disease-associated antigen.In some embodiments, the disease-associated antigen is an antigen of a pathogen. The pathogen may be prokaryotic (bacteria), eukaryotic (e.g., protozoan, helminth, fungus), virus or prion. In some embodiments, the pathogen is an intracellular pathogen. In some embodiments the pathogen is a virus. In some embodiments the pathogen is a bacterium.In some embodiments, the target antigen is a cancer-associated antigen. A cancer-associated antigen is an antigen whose expression or overexpression is associated with cancer. In some embodiments, the cancer-associated antigen is a receptor molecule, e.g., a cell surface receptor. In some embodiments, the cancer-associated antigen is a cell signalling molecule, e.g., a cytokine, chemokine, interferon, interleukin or lymphokine. In some embodiments, the cancer-associated antigen is a growth factor or a hormone. In some embodiments, the cancer-associated antigen is a viral antigen. A cancer cell antigen may be abnormally expressed by a cancer cell (e.g., the cancer cell antigen may be expressed with abnormal localisation), or may be expressed with an abnormal structure by a cancer cell. A cancer cell antigen may be capable of eliciting an immune response. In some embodiments, the antigen is expressed at the cell surface of the cancer cell ( / .e., the cancer cell antigen is a cancer cell surface antigen). In some embodiments, the part of the antigen which is bound by an antigen-binding molecule described herein isdisplayed on the external surface of the cancer cell (i.e., is extracellular). In some embodiments, the part of the antigen which is bound by an antigen-binding molecule described herein is presented on the surface of the cancer cell by a major histocompatibility complex (MHC) molecule, e.g., an MHC molecule comprising an MHC class I a chain polypeptide encoded by a HLA allele. The cancer cell antigen may be a cancer-associated antigen. In some embodiments the cancer cell antigen is an antigen whose expression is associated with the development, progression or severity of symptoms of a cancer. The cancer-associated antigen may be associated with the cause or pathology of the cancer, or may be expressed abnormally as a consequence of the cancer. In some embodiments, the cancer cell antigen is an antigen whose expression is upregulated (e.g., at the RNA and / or protein level) by cells of a cancer, e.g., as compared to the level of expression by comparable non-cancerous cells (e.g., non-cancerous cells derived from the same tissue / cell type). In some embodiments, the cancer-associated antigen may be preferentially expressed by cancerous cells, and not expressed by comparable non-cancerous cells (e.g., non-cancerous cells derived from the same tissue / cell type). In some embodiments, the cancer- associated antigen may be the product of a mutated oncogene or mutated tumor suppressor gene. In some embodiments, the cancer-associated antigen may be the product of an overexpressed cellular protein, a cancer antigen produced by an oncogenic virus, an oncofetal antigen, or a cell surface glycolipid or glycoprotein.Cancer-associated antigens are reviewed by Zarour HM, DeLeo A, Finn OJ, et al. Categories of Tumor Antigens. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6thedition. Hamilton (ON): BC Decker; 2003. Cancer-associated antigens include oncofetal antigens: CEA, Immature laminin receptor, TAG-72; oncoviral antigens such as HPV E6 and E7; overexpressed proteins: fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium- activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin; cancer-testis antigens: BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , PRAME, SSX-2; lineage restricted antigens: MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1 R, prostate specific antigen; mutated antigens: -catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF- PRII; post-translational ly altered antigens: MUC1 , idiotypic antigens: Ig, TCR. Other cancer cell antigens include heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B. In some embodiments the cancer cell antigen is a cancer cell antigen described in Zhao and Cao, Front Immunol. (2019) 10:2250, which is hereby incorporated by reference in its entirety.In some embodiments, an antigen / epitope / antigen-derived peptide is presented by a major histocompatibility complex (MHC) molecule. In some embodiments, an antigen / epitope / antigen-derived peptide is presented by a major histocompatibility complex (MHC) molecule comprising an MHC class I a chain polypeptide encoded by a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F or HLA-G allele.In some embodiments, an antigen / epitope / antigen-derived peptide is present in a peptide:MHC complex comprising an MHC class I a chain polypeptide, e.g., an MHC class I a chain polypeptide encoded by a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F or HLA-G allele.In some embodiments, the antigen is WT-1 . In some embodiments, the antigen is derived from WT-1 , i.e., a WT-1 -derived peptide.WT-1 (Wilms’ Tumor Antigen 1 ) is the protein identified by UniProtKB: P19544. The canonical isoform of human WT-1 has the amino acid sequence of P19544-1 (v2, 1991-08-01 ; SEQ ID NO:169). Alternative initiation sites and alternative splicing of mRNA encoded by the human WT1 gene yields eight main isoforms: isoform 1 (SEQ ID NO:169), isoform 2 (SEQ ID NO:184), isoform 3 (SEQ ID NO:185), isoform 4 (SEQ ID NO:186), isoform 6 (SEQ ID NO:187), isoform 7 (SEQ ID NO:188), isoform 8 (SEQ ID NO:189), isoform 9 (SEQ ID NO: 190). Isoform 1 has the amino acid sequence of SEQ ID NO: 169. Isoform 2 differs from isoform 1 in that positions 250-266 and 408-410 are absent. Isoform 3 differs from isoform 1 in that positions 250-266 are missing. Isoform 4 differs from isoform 1 in that positions 408 to 410 are missing. Isoform 6 differs from isoform 1 in that positions 1 to 144 and 408 to 410 are absent, and positions 145 to 147 are replaced with a different sequence of amino acids. Isoform 7 differs from isoform 1 in that it has an extended N-terminus with 73 additional amino acids. Isoform 8 differs from isoform 1 in that positions 250 to 266 are absent and in that it has an extended N-terminus with 73 additional amino acids. Isoform 9 differs from isoform 1 in that positions 1 to 144 and 250 to 266 are absent, and in that positions 145 to 147 are replaced with a different sequence of amino acids.WT-1 is a zinc finger transcription factor whose expression in normal adult tissue is rare but is overexpressed in leukemias of multiple lineages and a wide range of solid tumours. WT-1 comprises four zinc fing...

Claims

1. Claims1 . An immune cell comprising an exogenous T cell receptor (TCR) for use in a method of treating a disease or condition, wherein the method comprises administering a T cell modulatory polypeptide (TMP) capable of binding to and activating the immune cell comprising the exogenous TCR, wherein the TMP binds to the immune cell and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell.

2. A T cell modulatory polypeptide (TMP) for use in a method of treating a disease or condition, wherein the method comprises administering an immune cell comprising an exogenous T cell receptor (TCR) capable of binding to an antigen, and wherein the TMP is capable of binding to and activating the immune cell comprising the exogenous TCR, wherein the TMP binds to the immune cell and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell, optionally wherein the method does not include a regimen of lymphodepletion prior to administration of the immune cell comprising an exogenous T cell receptor.

3. Use of an immune cell comprising an exogenous T cell receptor (TCR) capable of binding to an antigen in the manufacture of a medicament for use in a method of treating a disease or condition, wherein the method comprises administering a T cell modulatory polypeptide (TMP) capable of binding to and activating the immune cell comprising the exogenous TCR, wherein the TMP binds to the immune cell and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell, optionally wherein the method does not include a regimen of lymphodepletion prior to administration of the immune cell comprising an exogenous T cell receptor.

4. Use of a T cell modulatory polypeptide (TMP) in the manufacture of a medicament for use in a method of treating a disease or condition, wherein the method comprises administering an immune cell comprising an exogenous T cell receptor (TCR) capable of binding to an antigen, and wherein the TMP is capable of binding to and activating the immune cell comprising the exogenous TCR, wherein the TMP binds to the immune cell and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell, optionally wherein the method does not include a regimen of lymphodepletion prior to administration of the immune cell comprising an exogenous T cell receptor.

5. A method of treating a disease or condition, comprising administering to a subject a therapeutically- or prophylactically-effective amount of (I) an immune cell comprising an exogenous T cell receptor (TCR) capable of binding to an antigen and (II) a T cell modulatory polypeptide (TMP) capable of binding to and activating the immune cell comprising the exogenous TCR, wherein the TMP binds to the immune cell and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell, optionally wherein the method does not include a regimen of lymphodepletion prior to administration of the immune cell comprising an exogenous T cell receptor.

6. A method of expanding a population of immune cells comprising an exogenous T cell receptor (TCR) capable of binding to an antigen, the method comprising contacting in vitro or in vivo the population of immune cells with a T cell modulatory polypeptide (TMP) capable of binding to and activating the immune cell comprising the exogenous TCR, and wherein the TMP comprises one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell comprising the exogenous TCR.

7. A method of selectively delivering an immunomodulatory polypeptide to a target immune cell comprising an exogenous T cell receptor (TCR) capable of binding an antigen, the method comprising contacting in vitro or in vivo, a mixed population of immune cells with a T-cell modulatory polypeptide (TMP), wherein the mixed population of immune cells comprises the target immune cell, wherein the TMP comprises (I) a peptide-MHC complex that specifically binds the exogenous TCR, and (II) one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell comprising the exogenous TCR.

8. A pharmaceutical combination, comprising (I) an immune cell comprising an exogenous T cell receptor (TCR) capable of binding to an antigen and (II) a T-cell modulatory polypeptide (TMP), wherein the TMP comprises (I) a peptide-MHC complex that specifically binds the exogenous TCR, and (II) one or more immunomodulatory polypeptides that stimulate activation and / or proliferation of the immune cell comprising the exogenous TCR.

9. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-8, wherein the TCR is capable of binding to a disease-associated antigen.

10. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-9, wherein the TCR is capable of binding to a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1 R, prostate specific antigen, p-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF- RII, MUC1 , heatshock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL- 2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.11 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-10, wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.

12. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-11 , wherein the TCR is capable of binding to an antigen-derived peptide.

13. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-12, wherein the TCR is capable of binding to an antigen-derived peptide when the antigen- derived peptide is presented by an MHC class I molecule, optionally an MHC molecule comprising an MHC class I a chain polypeptide.

14. The agent for use, the use, the method, or the pharmaceutical combination according to claim 13, wherein the antigen-derived peptide comprises or consists of the amino acid sequence of:(i) SEQ ID NO:1 , 179, 180, 181 or 182, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, optionally an HLA-A*02:01 allele;(ii) SEQ ID NO:191 or 223, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, optionally an HLA-A*02:01 allele; or(iii) SEQ ID NO:225 or 226, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, optionally an HLA-A*02:01 allele; or(iv) SEQ ID NO:227 or 228, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by an HLA-A*24 allele, optionally an HLA-A*24:02 allele.

15. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-14, wherein the TCR is capable of binding to a cancer-associated antigen, wherein the cancer-associated antigen is WT-1 .

16. The agent for use, the use, the method, or the pharmaceutical combination according to claim 15, wherein the TCR is capable of binding to an antigen-derived peptide, wherein the antigen-derived peptide comprises or consists of the amino acid sequence of:(v) SEQ ID NO: 1 , 179, 180, 181 or 182, optionally wherein the antigen-derived peptide is presented by an MHC molecule comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, optionally an HLA-A*02:01 allele.

17. The agent for use, the use, the method, or the pharmaceutical combination according to claim 15 or claim 16, wherein the exogenous TCR comprises:(a) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:34; in combination with (ii) a TCRp variable domain comprising a CDR3 having an amino acid sequence of SEQ ID NO:37;(b) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NQ:10; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:13;(c) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:4; in combination with (ii) a TCRp variable domain comprising a CDR30 having an amino acid sequence of SEQ ID NO:7;(d) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:16; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:19;(e) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:22; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:25;(f) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:28; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:31 ;(g) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:40; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:43;(h) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:46; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:49;(i) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO: 194; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:197;(j) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:231; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:234;(k) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:237; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NQ:240;(l) (I) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:243; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:246;(m) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:249; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:252;(n) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:255; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:258;(o) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:261; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NO:264; or(p) (i) a TCRa variable domain comprising a CDR3a having an amino acid sequence of SEQ ID NO:267; in combination with (ii) a TCRp variable domain comprising a CDR3P having an amino acid sequence of SEQ ID NQ:270.

18. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-17, wherein the exogenous TCR comprises:(a)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:32 CDR2a having the amino acid sequence of SEQ ID NO:33CDR3a having the amino acid sequence of SEQ ID NO:34, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:35 CDR2P having the amino acid sequence of SEQ ID NO:36 CDR3P having the amino acid sequence of SEQ ID NO:37;(b)(I) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:8CDR2a having the amino acid sequence of SEQ ID NO:9CDR3a having the amino acid sequence of SEQ ID NO: 10, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:11 CDR2P having the amino acid sequence of SEQ ID NO: 12 CDR3P having the amino acid sequence of SEQ ID NO: 13;(c)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:2CDR2a having the amino acid sequence of SEQ ID NO:3CDR3a having the amino acid sequence of SEQ ID NO:4, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:5 CDR2P having the amino acid sequence of SEQ ID NO:6 CDR3P having the amino acid sequence of SEQ ID NO:7;(d)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:14 CDR2a having the amino acid sequence of SEQ ID NO: 15CDR3a having the amino acid sequence of SEQ ID NO: 16, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO: 17 CDR2P having the amino acid sequence of SEQ ID NO: 18 CDR3P having the amino acid sequence of SEQ ID NO: 19;(e)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NQ:20CDR2a having the amino acid sequence of SEQ ID NO:21CDR3a having the amino acid sequence of SEQ ID NO:22, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:23 CDR2P having the amino acid sequence of SEQ ID NO:24 CDR3P having the amino acid sequence of SEQ ID NO:25;(f)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:26CDR2a having the amino acid sequence of SEQ ID NO:27CDR3a having the amino acid sequence of SEQ ID NO:28, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:29 CDR2P having the amino acid sequence of SEQ ID NQ:30 CDR3P having the amino acid sequence of SEQ ID NO:31 ;(g)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:38CDR2a having the amino acid sequence of SEQ ID NO:39CDR3a having the amino acid sequence of SEQ ID NQ:40, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:41 CDR2P having the amino acid sequence of SEQ ID NO:42 CDR3P having the amino acid sequence of SEQ ID NO:43;(h)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:44CDR2a having the amino acid sequence of SEQ ID NO:45CDR3a having the amino acid sequence of SEQ ID NO:46, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:47 CDR2P having the amino acid sequence of SEQ ID NO:48 CDR3P having the amino acid sequence of SEQ ID NO:49;(i)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO: 192CDR2a having the amino acid sequence of SEQ ID NO: 193CDR3a having the amino acid sequence of SEQ ID NO: 194, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO: 195 CDR2P having the amino acid sequence of SEQ ID NO: 196 CDR3P having the amino acid sequence of SEQ ID NO:197;0)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:229 CDR2a having the amino acid sequence of SEQ ID NO:230CDR3a having the amino acid sequence of SEQ ID NO:231 , and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:232 CDR2P having the amino acid sequence of SEQ ID NO:233 CDR3P having the amino acid sequence of SEQ ID NO:234;(k)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:235 CDR2a having the amino acid sequence of SEQ ID NO:236CDR3a having the amino acid sequence of SEQ ID NO:237, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRip having the amino acid sequence of SEQ ID NO:238 CDR2P having the amino acid sequence of SEQ ID NO:239 CDR3P having the amino acid sequence of SEQ ID NO:240;(l)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:241 CDR2a having the amino acid sequence of SEQ ID NO:242CDR3a having the amino acid sequence of SEQ ID NO:243, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NO:244 CDR2 having the amino acid sequence of SEQ ID NO:245 CDR3P having the amino acid sequence of SEQ ID NO:246;(m)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:247 CDR2a having the amino acid sequence of SEQ ID NO:248 CDR3a having the amino acid sequence of SEQ ID NO:249, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDRi having the amino acid sequence of SEQ ID NQ:250 CDR2P having the amino acid sequence of SEQ ID NO:251 CDR3P having the amino acid sequence of SEQ ID NO:252;(n)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:253 CDR2a having the amino acid sequence of SEQ ID NO:254 CDR3a having the amino acid sequence of SEQ ID NO:255, and / or(ii) a TCRp chain variable domain incorporating the following CDRs:CDR10 having the amino acid sequence of SEQ ID NO:256 CDR20 having the amino acid sequence of SEQ ID NO:257 CDR30 having the amino acid sequence of SEQ ID NO:258;(o)(I) a TCRa chain variable domain incorporating the following CDRs: CDR1a having the amino acid sequence of SEQ ID NO:259 CDR2a having the amino acid sequence of SEQ ID NQ:260 CDR3a having the amino acid sequence of SEQ ID NO:261 , and / or(ii) a TCR0 chain variable domain incorporating the following CDRs: CDR10 having the amino acid sequence of SEQ ID NO:262 CDR20 having the amino acid sequence of SEQ ID NO:263 CDR30 having the amino acid sequence of SEQ ID NO:264; or(P)(i) a TCRa chain variable domain incorporating the following CDRs:CDR1a having the amino acid sequence of SEQ ID NO:265 CDR2a having the amino acid sequence of SEQ ID NO:266 CDR3a having the amino acid sequence of SEQ ID NO:267, and / or(ii) a TCR0 chain variable domain incorporating the following CDRs:CDR10 having the amino acid sequence of SEQ ID NO:268 CDR20 having the amino acid sequence of SEQ ID NO:269 CDR30 having the amino acid sequence of SEQ ID NQ:270.

19. The agent for use, the use, the method, or the pharmaceutical combination according to claim 15, wherein the exogenous TCR comprises:(a) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NQ:60; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:61 ;(b) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:52; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:53;(c) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NQ:50; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:51 ;(d) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:54; in combination with (ii) a TCR0 variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:55;(e) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:56; in combination with (ii) a TCR0 variabledomain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:57;(f) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:58; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:59;(g) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:62; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:63;(h) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:64; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:65;(i) (I) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 198; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:199;(j) (I) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:271 ; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:272;(k) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:273; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:274;(l) (I) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:275; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:276;(m) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:277; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:278;(n) (I) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:279; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:280;(o) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:281 ; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:282; or(p) (i) a TCRa variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:283; in combination with (ii) a TCRp variable domain comprising an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO:284.

20. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-19, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of SEQ ID NO:1 , 179, 180, 181 or 182.21 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-20, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele (e.g., HLA-A*02:01 ), and a peptide comprising or consisting of VLDFAPPGA (SEQ ID NO:1 ).

22. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-20, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, and a peptide comprising or consisting of VLDFX1PPX2X3 (SEQ ID NO: 179), optionallywherein the exogenous TCR, or a fragment thereof, is capable of binding to a VLDFX1PPX2X3 (SEQ ID NO:179)-HLA- A*02:01 peptide:MHC complex, further optionally wherein Xi is A or any amino acid other than A, X2 is G or any amino acid other than G, and / or X3 is A or any amino acid other than A, and optionally wherein the exogenous TCR is TCR A0427.

23. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-20, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, and a peptide comprising or consisting of VLDFX1X2PX3X4 (SEQ ID NO: 180), optionally wherein the exogenous TCR, or a fragment thereof, is capable of binding to a VLDFX1X2PX3X4 (SEQ ID NO: 180)- HLA-A*02:01 peptide:MHC complex, further optionally wherein Xi is A or any amino acid other than A, X2 is P or any amino acid other than P, X3 is G or any amino acid other than G, and / or X4 is A or any amino acid other than A, and optionally wherein the exogenous TCR is TCR_A0429.

24. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-20, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, and a peptide comprising or consisting of VX1DFX2X3PX4X5 (SEQ ID NO:181 ), optionally wherein the exogenous TCR, or a fragment thereof, is capable of binding to a VX1DFX2X3PX4X5 (SEQ ID NO: 181 )- HLA-A*02:01 peptide:MHC complex, further optionally wherein Xi is L or any amino acid other than L, X2 is A or any amino acid other than A, X3 is P or any amino acid other than P, X4 is G or any amino acid other than G, and / or X5 is A or any amino acid other than A, and optionally wherein exogenous TCR is TCR A0431.

25. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 15-20, wherein the exogenous TCR, or a fragment thereof, is capable of binding to a peptide:MHC complex comprising an MHC class I a chain polypeptide encoded by an HLA-A*02 allele, and a peptide comprising or consisting of VLDFX1PX2GX3 (SEQ ID NO:182), optionally wherein the exogenous TCR, or a fragment thereof, is capable of binding to a VLDFX1PX2GX3 (SEQ ID NO:182)-HLA- A*02:01 peptide:MHC complex, further optionally wherein Xi is A or any amino acid other than A, X2 is P or any amino acid other than P, and / or X3 is A or any amino acid other than A, and optionally wherein the exogenous TCR is TCR A0432.

26. The agent for use, the use, or the method according to any one of claims 15-25, wherein the disease or condition is a WT1 + cancer.

27. The agent for use, the use, or the method according to claim 26, wherein the WT 1 + cancer is a hematologic (blood) cancer, a solid tumor, a central nervous system cancer, a neuroendocrine tumor, a germ cell tumor, or a sarcoma.

28. The agent for use, the use, or the method according to claim 26 or 27, wherein the immune cell comprising an exogenous T cell receptor and the TMP are administered to an individual who (I) had no prior therapies following an initial diagnosis of WT1 + cancer, (ii) had at least one prior therapy following an initial diagnosis of WT1 + cancer and was determined to have progressive disease, (ill) is receiving the composition as a first line treatment following a diagnosis of recurrent and / or metastatic WT1 + cancer, (iv) is receiving the composition as a second line or beyond therapy following a diagnosis of recurrent and / or metastatic WT1+ cancer and a diagnosis of progressive disease following the patient’s prior line of treatment, or (v) has become refractory to a prior treatment for a WT1 + cancer, has failed to respond to a prior treatment for a WT1 + cancer, and / or has been determined to have progressive disease following a prior treatment for a WT1 + cancer, optionally wherein the determination of progressive disease is based on RECIST 1.1 criteria, IRECIST criteria, or IrRECIST criteria.

29. The agent for use, the use, or the method according to any one of claims 26-28, wherein the disease or condition is a newly diagnosed or a recurrent and / or metastatic WT1 + cancer selected from selected from a leukemia, a desmoplastic small round cell tumor, a gastric cancer, a colon cancer, a lung cancer, a breast cancer, a germ cell tumor, an ovarian cancer, a uterine cancer, a thyroid cancer, a liver cancer, a renal cancer, a Kaposi's sarcoma, a sarcoma, a hepatocellular carcinoma, a Wilms' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), a non-small cell lung cancer (NSCLC), a myeloma, pancreatic cancer, colorectal cancer, a mesothelioma, glioblastoma (also called glioblastoma multiforme or ‘GBM’), a soft tissue sarcoma, a neuroblastoma, and a nephroblastoma.

30. The agent for use, the use, or the method according to claim 29, wherein the disease or condition is a non-small cell lung cancer (NSCLC), pancreatic cancer, gastric cancer, colorectal cancer, ovarian cancer, GBM or hepatoblastoma.31 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP comprises: i) a peptide epitope; ii) a first major histocompatibility complex (MHC) class I polypeptide, wherein the first MHC class I polypeptide is a p2-microglobulin ( 2M) polypeptide; ill) one or more immunomodulatory polypeptides; iv) a second MHC class I polypeptide, wherein the second MHC class I polypeptide is a MHC class I heavy chain polypeptide; and v) a scaffold polypeptide, optionally an immunoglobulin (Ig) Fc polypeptide, and wherein the TMP presents a peptide:MHC complex comprising the MHC class I heavy chain polypeptide and the peptide epitope, and . wherein the TMP may comprise one or more independently selected peptide linkers between any two of the component polypeptides, and wherein when the TMP comprises more than one immunomodulatory polypeptide, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.

32. The agent for use, the use, the method, or the pharmaceutical combination according to claim 31 , wherein the scaffold is a variant Ig Fc polypeptide comprising one or more amino acid substitutions that reduce or substantially eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC).

33. The agent for use, the use, the method, or the pharmaceutical combination according to claim 31 or claim 32, wherein at least one of the one or more immunomodulatory polypeptides is an activating polypeptide, optionally wherein the activating polypeptide is a wild type or variant polypeptide selected from a 4-1 BBL polypeptide, a CD80 polypeptide, a CD86 polypeptide, an IL-2 polypeptide, an IL-7 polypeptide, an IL-12 polypeptide, an IL-15 polypeptide, an IL-21 polypeptide, an ICOS polypeptide, an 0x40 polypeptide or a CD40 polypeptide.

34. The agent for use, the use, the method, or the pharmaceutical combination according to claim 33, wherein the activating polypeptide is a variant IL-2 polypeptide.

35. The agent for use, the use, the method, or the pharmaceutical combination according to claim 34, wherein the variant IL-2 polypeptide exhibits decreased binding to IL-2Ra and / or IL-2R .

36. The agent for use, the use, the method, or the pharmaceutical combination according to claim 35, wherein the variant IL-2 immunomodulatory polypeptide exhibits decreased binding to IL-2Ra and IL-2R .

37. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 34-36, wherein the amino acid sequence of the variant IL-2 polypeptide has a percent sequence identity that is at least 95%, at least 96%, at least 97%, or at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:375.

38. The agent for use, the use, the method, or the pharmaceutical combination according to claim 37, wherein amino acid 16 is an amino acid other than histidine and / or amino acid 42 is an amino acid other than phenylalanine, optionally wherein amino acid 16 is an amino acid other than histidine and amino acid 42 is an amino acid other than phenylalanine.

39. The agent for use, the use, the method, or the pharmaceutical combination according to claim 38, wherein amino acid 16 is Ala, Thr, Asp or Glu, and / or wherein amino acid 42 is Ala, optionally wherein amino acid 16 is Ala and / or amino acid 42 is Ala.

40. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 34-39, wherein the TMP comprises two variant IL-2 polypeptides, optionally wherein the two variant IL-2 polypeptides have the same amino acid sequence.41 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 34-40, wherein the TMP comprises two variant IL-2 polypeptides in tandem, wherein the two variant IL-2 polypeptides have the same amino acid sequence, and optionally are connected by a linker.

42. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 31-41 , wherein the TMP is a heterodimer that comprises: a) a first polypeptide comprising: i) the peptide epitope; andII) the p2-microglobulin ( 2M) polypeptide; and b) a second polypeptide comprising: i) the one or more immunomodulatory polypeptides; ii) the MHC class I heavy chain polypeptide; and ill) an immunoglobulin (Ig) Fc polypeptide, wherein the TMP may comprise one or more independently selected peptide linkers between any two of the component polypeptides, and wherein when the TMP comprises more than one immunomodulatory polypeptide, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.

43. The agent for use, the use, the method, or the pharmaceutical combination according to claim 42, wherein the TMP is a heterodimer that comprises: a1 ) a first polypeptide comprising, in the N-terminal to C-terminal direction: i) the peptide epitope; ii) a peptide linker; and ill) the [32M polypeptide; and b1 ) a second polypeptide comprising, in the N-terminal to C-terminal direction: i) the one or more immunomodulatory polypeptides; ii) an optional linker; ill) the MHC class I heavy chain polypeptide; iv) an optional linker; andv) the Ig Fc polypeptide, or a2) a first polypeptide comprising, in the N-terminal to C-terminal direction : i) the peptide epitope; ii) a peptide linker; and ill) the [32M polypeptide; and b2) a second polypeptide comprising, in the N-terminal to C-terminal direction:I) the MHC class I heavy chain polypeptide; ii) an optional linker; ill) the Ig Fc polypeptide; iv) an optional linker; and v) the one or more immunomodulatory polypeptides, wherein, when the TMP comprises more than one immunomodulatory polypeptide in tandem, the immunomodulatory polypeptides may be connected by one or more independently selected peptide linkers.

44. The agent for use, the use, the method, or the pharmaceutical combination according to claim 42 or claim 43, wherein the heterodimer comprises a disulfide bond formed between a Cys residue in the 02M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide.

45. The agent for use, the use, the method, or the pharmaceutical combination according to claim 42 or claim 43, wherein the first polypeptide comprises a Cys-containing linker interposed between the peptide epitope and the 02 M polypeptide, and wherein the heterodimer comprises a disulfide bond formed between the Cys residue in the Cys- containing linker and a Cys residue in the MHC class I heavy chain polypeptide.

46. The agent for use, the use, the method, or the pharmaceutical combination according to claim 45, wherein the first polypeptide and the second polypeptide are covalently linked to one another by a second disulfide bond, wherein the second disulfide is bond formed between a Cys residue in the 02M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide.

47. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 42-46, wherein a) the first polypeptide of each heterodimer comprises, in order from N-terminus to C-terminus:I) the peptide epitope, wherein the peptide has a length of 8-20 amino acids; ii) a peptide linker; and ill) the [32M polypeptide; b) the second polypeptide of each heterodimer comprises, in the N-terminal to C-terminal direction:I) the first variant IL-2 polypeptide; ii) a second variant IL-2 polypeptide; ill) the MHC class I heavy chain polypeptide; and iv) the Ig Fc polypeptide,wherein each variant IL-2 polypeptide has at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is an amino acid other than histidine and amino acid 42 is an amino acid other than phenylalanine, and wherein the second polypeptide comprises an independently selected peptide linker between one or more of: a) the first immunomodulatory polypeptide and the second immunomodulatory polypeptide; b) the second immunomodulatory polypeptide and the MHC class I heavy chain polypeptide; and c) the MHC class I heavy chain polypeptide and the Ig Fc polypeptide.

48. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 42-46, wherein a) the first polypeptide of each heterodimer comprises, in order from N-terminus to C-terminus:I) the peptide epitope, wherein the peptide has a length of 8-20 amino acids; ii) a peptide linker; andHi) the 02M polypeptide; b) the second polypeptide of each heterodimer comprises, in the N-terminal to C-terminal direction:I) the MHC class I heavy chain polypeptide; ii) the Ig Fc polypeptide; ill) the first variant IL-2 polypeptide; and iv) a second variant IL-2 polypeptide, wherein the scaffold is a variant Ig Fc polypeptide comprising one or more amino acid substitutions that reduce or substantially eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC), wherein each variant IL-2 polypeptide has at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is an amino acid other than histidine and amino acid 42 is an amino acid other than phenylalanine, and wherein the second polypeptide comprises an independently selected peptide linker between one or more of: a) the MHC class I heavy chain polypeptide and the Ig Fc polypeptide b) the Ig Fc polypeptide the first immunomodulatory polypeptide; and c) the first immunomodulatory polypeptide and the second immunomodulatory polypeptide.

49. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 42-48, wherein the peptide epitope is an epitope of a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1R, prostate specific antigen, -catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF- RII, MUC1, heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphataseplacental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.

50. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 42-48, wherein the peptide epitope is an epitope of a cancer-associated antigen selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.51 . The agent for use, the use, the method, or the pharmaceutical combination according to claim 50, wherein the peptide epitope is a WT1 peptide.

52. The agent for use, the use, the method, or the pharmaceutical combination according to claim 51 , wherein the peptide epitope is a WT1 peptide selected from CMTWNQMNLGATLKG (SEQ ID NO:378), WNQMNLGATLKGVAA (SEQ ID NO:379), CMTWNYMNLGATLKG (SEQ ID NQ:380), WNYMNLGATLKGVAA (SEQ ID NO:381), MTWNQMNLGATLKGV (SEQ ID NO:382), TWNQMNLGATLKGVA (SEQ ID NO:383), CMTWNLMNLGATLKG (SEQ ID NO:384), MTWNLMNLGATLKGV (SEQ ID NO:385), TWNLMNLGATLKGVA (SEQ ID NO:386), WNLMNLGATLKGVAA (SEQ ID NO:387), MNLGATLK (SEQ ID NO:388), MTWNYMNLGATLKGV (SEQ ID NO:389), TWNYMNLGATLKGVA (SEQ ID NQ:390), CMTWNQMNLGATLKGVA (SEQ ID NO:391), CMTWNLMNLGATLKGVA (SEQ ID NO:392), CMTWNYMNLGATLKGVA (SEQ ID NO:393), GYLRNPTAC (SEQ ID NO:394), GALRNPTAL (SEQ ID NO:395), YALRNPTAC (SEQ ID NO:396), GLLRNPTAC (SEQ ID NO:397), RYRPHPGAL (SEQ ID NO:398), YQRPHPGAL (SEQ ID NO:399), RLRPHPGAL (SEQ ID NQ:400), RIRPHPGAL (SEQ ID NQ:401), QFPNHSFKHEDPMGQ (SEQ ID NQ:402), HSFKHEDPY (SEQ ID NQ:403), QFPNHSFKHEDPM (SEQ ID NQ:404), QFPNHSFKHEDPY (SEQ ID NQ:405), KRPFMCAYPGCNK (SEQ ID NQ:406), KRPFMCAYPGCYK (SEQ ID NQ:407), FMCAYPGCY (SEQ ID NQ:408), FMCAYPGCK (SEQ ID NQ:409), KRPFMCAYPGCNKRY (SEQ ID NQ:410), SEKRPFMCAYPGCNK (SEQ ID NO:411), KRPFMCAYPGCYKRY (SEQ ID NO:412), NLMNLGATL (SEQ ID NO:413), VLDFAPPGA (SEQ ID NO:1); RMFPNAPYL (SEQ ID NO:414);CMTWNQMN (SEQ ID NO:415); CYTWNQMNL (SEQ ID NO:416); NYMNLGATL (SEQ ID NO:417); YMFPNAPYL (SEQ ID NO:418); SLGEQQYSV (SEQ ID NO:419); CMTWNQMNL (SEQ ID NQ:420); and NQMNLGATL (SEQ ID NO:421 ), optionally wherein the WT-1 peptide present in a TMP is CMTWNQMN (SEQ ID NO:415) or CYTWNQMNL (SEQ ID NO:416).

53. The agent for use, the use, the method, or the pharmaceutical combination according to claim 51 , wherein the peptide epitope is a WT1 peptide selected from CMTWNQMN (SEQ ID NO:415); NYMNLGATL (SEQ ID NO:417) (WT-1 239-247; Q240Y); CYTWNQMNL (SEQ ID NO:416) (WT-1 235- 243); CMTWNQMNL (SEQ ID NQ:420) (WT-1 235-243); NQMNLGATL (SEQ ID NO:421 ) (WT-1 239- 247); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA -A*24 allele, optionally an HLA-A*24:02 allele.

54. The agent for use, the use, the method, or the pharmaceutical combination according to claim 51 , wherein the peptide epitope is a WT1 peptide selected from VLDFAPPGA (SEQ ID NO:1 ) (WT-1 37-45); RMFPNAPYL (SEQ ID NO:414) (WT-1 126-134); YMFPNAPYL (SEQ ID NO:418) (WT-1 126-134;R126Y); SLGEQQYSV (SEQ ID NO:419) (WT-1 187-195); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA -A*02 allele, optionally an HLA-A*02:01 allele.

55. The agent for use, the use, the method, or the pharmaceutical combination according to claim 52, wherein the WT1 peptide comprises or consists of VLDFAPPGA (SEQ ID NO:1 ).

56. The agent for use, the use, the method, or the pharmaceutical combination according to claim 51 , wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:422 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:423, wherein the TMP comprises a first disulfide bond formed between (I) a Cys residue in the peptide linker between the WT1 peptide and the 2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide, and wherein the heterodimer comprises a second disulfide bond formed between a Cys residue in the 2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide.

57. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP is a dimeric TMP (a DTMP) comprising two heterodimeric TMPs according to any one of claims 42-56, and wherein one or more disulfide bonds link the Ig Fc polypeptide of one heterodimeric TMP to the Ig Fc polypeptide of the other heterodimeric TMP.

58. The agent for use, the use, the method, or the pharmaceutical combination according to claim 57, wherein the DTMP is a homodimer comprising two copies of a TMP according to any one of claims 42-56.

59. The agent for use, the use, the method, or the pharmaceutical combination according to claim 57, wherein the DTMP is a heterodimer comprising two different TMPs according to any one of claims 42-56.

60. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP is CUE-102, i.e., wherein the TMP is a dimeric TMP (a DTMP) comprising two copies of a heterodimeric TMPs according to claim 56, and wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.61 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-41 , wherein the TMP comprises a single-chain polypeptide, and wherein the single-chain polypeptide comprises from N-terminus to C-terminus:I) the peptide epitope; ii) a peptide linker;Hi) the 2M polypeptide; iv) an optional peptide linker; v) the MHC class I heavy chain polypeptide; vi) an optional peptide linker; vii) an immunoglobulin (Ig) Fc polypeptide;viii) an optional peptide linker; and lx) the one or more immunomodulatory polypeptides.

62. The agent for use, the use, the method, or the pharmaceutical combination according to claim 61 , wherein the one or more immunomodulatory polypeptides are one or two variant IL-2 polypeptides having an amino acid sequence that has at least 95%, at least 96%, at least 97%, or at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is an amino acid other than histidine and / or amino acid 42 is an amino acid other than phenylalanine.

63. The agent for use, the use, the method, or the pharmaceutical combination according to claim 52, wherein the TMP comprises two variant IL-2 polypeptides in tandem, optionally wherein the two polypeptides are joined by a peptide linker.

64. The agent for use, the use, the method, or the pharmaceutical combination according to claim 63, wherein each of the variant IL-2 polypeptides comprises the amino acid sequence set forth in SEQ ID NO:375 wherein amino acid 15 is Ala and amino acid 42 is Ala.

65. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 61-64, wherein the TMP comprises a Cys-containing peptide linker between the peptide epitope and the 2M polypeptide, and wherein the TMP comprises an intrachain disulfide bond between the Cys present in the peptide linker and a Cys in the MHC class I heavy chain polypeptide.

66. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 61-65, wherein the peptide epitope is an epitope of a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1R, prostate specific antigen, p-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF-pRII, MUC1, heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.

67. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 61-65, wherein the peptide epitope is an epitope of a cancer-associated antigen selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.

68. The agent for use, the use, the method, or the pharmaceutical combination according to claim 67, wherein the peptide epitope is a WT1 peptide.

69. The agent for use, the use, the method, or the pharmaceutical combination according to claim 68, wherein the peptide epitope is a WT1 peptide selected from CMTWNQMNLGATLKG (SEQ ID NO:378), WNQMNLGATLKGVAA (SEQ ID NO:379), CMTWNYMNLGATLKG (SEQ ID NQ:380), WNYMNLGATLKGVAA (SEQ ID NO:381), MTWNQMNLGATLKGV (SEQ ID NO:382), TWNQMNLGATLKGVA (SEQ ID NO:383), CMTWNLMNLGATLKG (SEQ ID NO:384), MTWNLMNLGATLKGV (SEQ ID NO:385), TWNLMNLGATLKGVA (SEQ ID NO:386), WNLMNLGATLKGVAA (SEQ ID NO:387), MNLGATLK (SEQ ID NO:388), MTWNYMNLGATLKGV (SEQ ID NO:389), TWNYMNLGATLKGVA (SEQ ID NQ:390), CMTWNQMNLGATLKGVA (SEQ ID NO:391), CMTWNLMNLGATLKGVA (SEQ ID NO:392), CMTWNYMNLGATLKGVA (SEQ ID NO:393), GYLRNPTAC (SEQ ID NO:394), GALRNPTAL (SEQ ID NO:395), YALRNPTAC (SEQ ID NO:396), GLLRNPTAC (SEQ ID NO:397), RYRPHPGAL (SEQ ID NO:398), YQRPHPGAL (SEQ ID NO:399), RLRPHPGAL (SEQ ID NQ:400), RIRPHPGAL (SEQ ID NQ:401), QFPNHSFKHEDPMGQ (SEQ ID NQ:402), HSFKHEDPY (SEQ ID NQ:403), QFPNHSFKHEDPM (SEQ ID NQ:404), QFPNHSFKHEDPY (SEQ ID NQ:405), KRPFMCAYPGCNK (SEQ ID NQ:406), KRPFMCAYPGCYK (SEQ ID NQ:407), FMCAYPGCY (SEQ ID NQ:408), FMCAYPGCK (SEQ ID NQ:409), KRPFMCAYPGCNKRY (SEQ ID NQ:410), SEKRPFMCAYPGCNK (SEQ ID NO:411 ), KRPFMCAYPGCYKRY (SEQ ID NO:412), NLMNLGATL (SEQ ID NO:413), VLDFAPPGA (SEQ ID NO:1); RMFPNAPYL (SEQ ID NO:414); CMTWNQMN (SEQ ID NO:415); CYTWNQMNL (SEQ ID NO:416); NYMNLGATL (SEQ ID NO:417);YMFPNAPYL (SEQ ID NO:418); SLGEQQYSV (SEQ ID NO:419); CMTWNQMNL (SEQ ID NQ:420); and NQMNLGATL (SEQ ID NO:421 ), optionally wherein the WT-1 peptide present in a TMP is CMTWNQMN (SEQ ID NO:415) or CYTWNQMNL (SEQ ID NO:416).

70. The agent for use, the use, the method, or the pharmaceutical combination according to claim 68, wherein the peptide epitope is a WT1 peptide selected from CMTWNQMN (SEQ ID NO:415); NYMNLGATL (SEQ ID NO:417) (WT-1 239-247; Q240Y); CYTWNQMNL (SEQ ID NO:416) (WT-1 235- 243); CMTWNQMNL (SEQ ID NQ:420) (WT-1 235-243); NQMNLGATL (SEQ ID NO:421 ) (WT-1 239- 247); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA -A*24 allele, optionally an HLA-A*24:02 allele.71 . The agent for use, the use, the method, or the pharmaceutical combination according to claim 68, wherein the peptide epitope is a WT1 peptide selected from VLDFAPPGA (SEQ ID NO:1 ) (WT-1 37-45); RMFPNAPYL (SEQ ID NO:414) (WT-1 126-134); YMFPNAPYL (SEQ ID NO:418) (WT-1 126-134; R126Y); SLGEQQYSV (SEQ ID NO:419) (WT-1 187-195); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA -A*02 allele, optionally an HLA-A*02:01 allele.

72. The agent for use, the use, the method, or the pharmaceutical combination according to claim 71 , wherein the WT1 peptide comprises or consists of VLDFAPPGA (SEQ ID NO:1 ).

73. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP is a dimeric TMP (DTMP) comprising two TMPs according to any one ofclaims 61-72, wherein the two TMPs are linked by one or more disulfide bonds that join the Ig Fc polypeptide of one TMP to the Ig Fc polypeptide of the other TMP.

74. The agent for use, the use, the method, or the pharmaceutical combination according to claim 73, wherein the two TMPs are identical, i.e., the DTMP is a homodimer, optionally wherein the two TMPs are linked by two disulfide bonds that join the Ig Fc polypeptide of one TMP to the Ig Fc polypeptide of the other TMP.

75. The agent for use, the use, the method, or the pharmaceutical combination according to claim 73, wherein the two TMPs are not identical, i.e., optionally wherein the two TMPs are linked by interspecific binding sequences.

76. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP comprises a peptide epitope that is conjugated to a chemical conjugation site in the TMP, optionally wherein the 2M polypeptide, the one or more immunomodulatory polypeptides, the class I MHC heavy chain polypeptide, the Ig Fc polypeptide, and linkers are in a single polypeptide chain, and optionally wherein the chemical conjugation site is a cysteine in the 2M polypeptide.

77. The agent for use, the use, the method, or the pharmaceutical combination according to claim 76, wherein the one or more immunomodulatory polypeptides are one or two variant IL-2 polypeptides having an amino acid sequence that has at least 95%, at least 96%, at least 97%, or at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is an amino acid other than histidine and / or amino acid 42 is an amino acid other than phenylalanine.

78. The agent for use, the use, the method, or the pharmaceutical combination according to claim 76 or 77, wherein the TMP comprises two variant IL-2 polypeptides in tandem, optionally wherein the two polypeptides are joined by a peptide linker.

79. The agent for use, the use, the method, or the pharmaceutical combination according to claim 78, wherein each of the variant IL-2 polypeptides comprises the amino acid sequence set forth in SEQ ID NO:375 wherein amino acid 15 is Ala and amino acid 42 is Ala.

80. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 76-79, wherein the peptide epitope is an epitope of a cancer-associated antigen, optionally wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1R, prostate specific antigen, -catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF- RII, MUC1, heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulatedprotein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.81 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 75-79, wherein the peptide epitope is an epitope of a cancer-associated antigen selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.

82. The agent for use, the use, the method, or the pharmaceutical combination according to claim 81 , wherein the peptide epitope is a WT1 peptide.

83. The agent for use, the use, the method, or the pharmaceutical combination according to claim 82, wherein the WT1 peptide is selected from CMTWNQMNLGATLKG (SEQ ID NO:378), WNQMNLGATLKGVAA (SEQ ID NO:379), CMTWNYMNLGATLKG (SEQ ID NQ:380), WNYMNLGATLKGVAA (SEQ ID NO:381), MTWNQMNLGATLKGV (SEQ ID NO:382), TWNQMNLGATLKGVA (SEQ ID NO:383), CMTWNLMNLGATLKG (SEQ ID NO:384), MTWNLMNLGATLKGV (SEQ ID NO:385), TWNLMNLGATLKGVA (SEQ ID NO:386), WNLMNLGATLKGVAA (SEQ ID NO:387), MNLGATLK (SEQ ID NO:388), MTWNYMNLGATLKGV (SEQ ID NO:389), TWNYMNLGATLKGVA (SEQ ID NQ:390), CMTWNQMNLGATLKGVA (SEQ ID NO:391), CMTWNLMNLGATLKGVA (SEQ ID NO:392), CMTWNYMNLGATLKGVA (SEQ ID NO:393), GYLRNPTAC (SEQ ID NO:394), GALRNPTAL (SEQ ID NO:395), YALRNPTAC (SEQ ID NO:396), GLLRNPTAC (SEQ ID NO:397), RYRPHPGAL (SEQ ID NO:398), YQRPHPGAL (SEQ ID NO:399), RLRPHPGAL (SEQ ID NQ:400), RIRPHPGAL (SEQ ID NQ:401), QFPNHSFKHEDPMGQ (SEQ ID NQ:402), HSFKHEDPY (SEQ ID NQ:403), QFPNHSFKHEDPM (SEQ ID NQ:404), QFPNHSFKHEDPY (SEQ ID NQ:405), KRPFMCAYPGCNK (SEQ ID NQ:406), KRPFMCAYPGCYK (SEQ ID NQ:407), FMCAYPGCY (SEQ ID NQ:408), FMCAYPGCK (SEQ ID NQ:409), KRPFMCAYPGCNKRY (SEQ ID NQ:410), SEKRPFMCAYPGCNK (SEQ ID NO:411 ), KRPFMCAYPGCYKRY (SEQ ID NO:412), NLMNLGATL (SEQ ID NO:413), VLDFAPPGA (SEQ ID NO:1); RMFPNAPYL (SEQ ID NO:414);CMTWNQMN (SEQ ID NO:415); CYTWNQMNL (SEQ ID NO:416); NYMNLGATL (SEQ ID NO:417); YMFPNAPYL (SEQ ID NO:418); SLGEQQYSV (SEQ ID NO:419); CMTWNQMNL (SEQ ID NQ:420); and NQMNLGATL (SEQ ID NO:421 ), optionally wherein the WT-1 peptide present in a TMP is CMTWNQMN (SEQ ID NO:415) or CYTWNQMNL (SEQ ID NO:416).

84. The agent for use, the use, the method, or the pharmaceutical combination according to claim 82, wherein the WT1 peptide is selected from CMTWNQMN (SEQ ID NO:415); NYMNLGATL (SEQ ID NO:417) (WT-1 239-247; Q240Y); CYTWNQMNL (SEQ ID NO:416) (WT-1 235-243); CMTWNQMNL (SEQ ID NQ:420) (WT-1 235-243); NQMNLGATL (SEQ ID NO:421 ) (WT-1 239-247); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA - A*24 allele, optionally an HLA-A*24:02 allele.

85. The agent for use, the use, the method, or the pharmaceutical combination according to claim 82, wherein the WT1 peptide is selected from VLDFAPPGA (SEQ ID NO:1 ) (WT-1 37-45); RMFPNAPYL(SEQ ID NO:414) (WT-1 126-134); YMFPNAPYL (SEQ ID NO:418) (WT-1 126-134; R126Y); SLGEQQYSV (SEQ ID NO:419) (WT-1 187-195); and NLMNLGATL (SEQ ID NO:413) (WT-1 239-247; Q240L), and wherein the MHC class I heavy chain allele is an HLA -A*02 allele, optionally an HLA- A*02:01 allele.

86. The agent for use, the use, the method, or the pharmaceutical combination according to claim 85, wherein the WT1 peptide comprises of consists of VLDFAPPGA (SEQ ID NO:1 ).

87. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP is a dimeric TMP (DTMP) comprising two TMPs according to any one of claims 76-86, wherein the two TMPs are linked by one or more disulfide bonds that join the Ig Fc polypeptide of one TMP to the Ig Fc polypeptide of the other TMP.

88. The agent for use, the use, the method, or the pharmaceutical combination according to claim 87, wherein the two TMPs are identical, i.e., the DTMP is a homodimer, optionally wherein the two TMPs are linked by two disulfide bonds that join the Ig Fc polypeptide of one TMP to the Ig Fc polypeptide of the other TMP.

89. The agent for use, the use, the method, or the pharmaceutical combination according to claim 87, wherein the two TMPs are not identical, i.e., optionally wherein the two TMPs are linked by interspecific binding sequences.

90. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP comprises an antibody or fragment thereof that binds to CD8+ T cells, optionally wherein the antibody or fragment thereof binds to CD3 or CD8.91 . The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-30, wherein the TMP comprises an antibody or fragment thereof that specifically binds to either the exogenous TCR of the immune cell or to another exogenous polypeptide expressed on the immune cell.

92. The agent for use, the use, the method, or the pharmaceutical combination according to claim 90 or 91 , wherein the TMP comprises one or more immunomodulatory polypeptides, wherein at least one of the one or more immunomodulatory polypeptides is an activating polypeptide, optionally wherein the activating polypeptide is a wild type or variant polypeptide selected from a 4-1 BBL polypeptide, a CD80 polypeptide, a CD86 polypeptide, an IL-2 polypeptide, an IL-7 polypeptide, an IL-12 polypeptide, an IL-15 polypeptide, an IL-21 polypeptide, an ICOS polypeptide, an 0x40 polypeptide or a CD40 polypeptide.

93. The agent for use, the use, the method, or the pharmaceutical combination according to claim 92, at least one of the one or more immunomodulatory polypeptides is a variant IL-2 polypeptide having an amino acid sequence that has at least 95%, at least 96%, at least 97%, or at least 98% sequence identityto the amino acid sequence set forth in SEQ ID NO:375, wherein amino acid 16 is an amino acid other than histidine and / or amino acid 42 is an amino acid other than phenylalanine.

94. The agent for use, the use, the method, or the pharmaceutical combination according to claim 92 or 93, wherein the TMP comprises two variant IL-2 polypeptides in tandem, optionally wherein the two polypeptides are joined by a peptide linker.

95. The agent for use, the use, the method, or the pharmaceutical combination according to claim 93 or 94, wherein each of the variant IL-2 polypeptides comprises the amino acid sequence set forth in SEQ ID NO:375 wherein amino acid 15 is Ala and amino acid 42 is Ala.

96. The agent for use, the use, the method, or the pharmaceutical combination according to any one of claims 1-95, wherein the TMP further comprises a targeting polypeptide that binds to a cancer- associated antigen.

97. The agent for use, the use, the method, or the pharmaceutical combination according to claim 96, wherein the cancer-associated antigen is selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4, PRAME, CEA, mucin-1 , Immature laminin receptor, TAG-72, HPV E6, HPV E7, fibroblast activation protein (FAP), B-cell maturation antigen (BCMA), CD19, HER2 / neu, BING-4, calcium-activated chloride channel 2, cyclin-B1 , 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP-1 , survivin, BAGE, CAGE, GAGE, MAGE, SAGE, XAGE, CT9, CT10, NY-ESO-1 , SSX-2, MARTI , Gp100, tyrosinase, TRP-1 / 2, MC1R, prostate specific antigen, |3-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, MART-2, p53, Ras, TGF-|3RII, MUC1, heat-shock protein 70 (HSP70), heat-shock protein 90 (HSP90), glucose-regulated protein 78 (GRP78), vimentin, nucleolin, feto-acinar pancreatic protein (FAPP), alkaline phosphatase placental-like 2 (ALPPL-2), siglec-5, stress-induced phosphoprotein 1 (STIP1 ), protein tyrosine kinase 7 (PTK7), and cyclophilin B.

98. The agent for use, the use, the method, or the pharmaceutical combination according to claim 96, wherein the cancer-associated antigen selected from WT-1 , MAGE-A1 , MAGE-A10, MAGE-A4 and PRAME.

99. The agent for use, the use, the method, or the pharmaceutical combination according to claim 98, wherein the cancer-associated antigen is WT1.

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