Combination therapies

Abstract

The present invention relates to novel combination therapies or pharmaceutical compositions and their use in the treatment of cancers, particularly cancers expressing carcinoembryonic antigen (CEA).

Description

[0001]COMBINATION THERAPIES Field of Invention The present invention relates to combination therapies, and their use medicine, including in the in the treatment of cancers, particularly cancers expressing carcinoembryonic antigen (CEA). The combination therapies or pharmaceutical compositions comprise (a) a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) a PD-1 inhibitor. The invention also relates to pharmaceutical compositions, uses of, methods of using the combination therapies of the invention. The cancer may be a solid tumour. Background Immunotherapy of cancer Cancer is a leading cause of premature deaths in the developed world. Immunotherapy of cancer aims to mount an effective immune response against tumour cells. This may be achieved by, for example, breaking tolerance against tumour antigen, augmenting anti-tumour immune responses, and stimulating local cytokine responses at the tumour site. The key effector cell of a long-lasting anti-tumour immune response is the activated tumour-specific effector T cell. Potent expansion of activated tumour-specific effector T cells can redirect the immune response towards the tumour. In this context, various immunosuppressive mechanisms induced by the tumour microenvironment suppress the activity of effector T cells. Several immunosuppressive mediators are expressed by the tumour cells. Such mediators inhibit T cell activation, either directly, or indirectly by inducing e.g. regulatory T cells (Treg) or myeloid-derived suppressor cells. Depleting, inhibiting, reverting or inactivating such regulatory cells may therefore provide anti-tumour effects and revert the immune suppression in the tumour microenvironment. Further, incomplete activation of effector T cells by, for example, dendritic cells (DC) can result in sub-optimally activated or anergic T cells, resulting in an inefficient anti-tumour response. In contrast, adequate induction by DC can generate a potent expansion of activated effector T cells, redirecting and enhancing the immune response towards the tumour. In addition, natural killer (NK) cells play an important role in tumour immunology by attacking tumour cells with down-regulated human leukocyte antigen (HLA) expression and by inducing antibody dependent cellular cytotoxicity (ADCC). Stimulation of NK cells may thus also reduce tumour growth. CD40 CD40, a 48 kDa transmembrane cell surface glycoprotein, is a co-stimulatory receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily (Banchereau J, Bazan F, Blanchard D, et al. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881-922; Elgueta R, Benson MJ, de Vries VC, et al. Molecular mechanism and function of CD40 / CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72). CD40 is expressed in diverse cell types and can be detected on antigen-presenting cells (APC), including dendritic cells (DC), B cells, and macrophages. In addition, CD40 is expressed on granulocytes, endothelial cells, smooth muscle cells, fibroblasts, and epithelial cells (Banchereau J, Bazan F, Blanchard D, et al. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881-922; Elgueta R, Benson MJ, de Vries VC, et al. Molecular mechanism and function of CD40 / CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72; Korniluk A, Kemona H, Dymicka-Piekarska V. Multifunctional CD40L: pro- and anti-neoplastic activity. Tumour Biol. 2014 Oct;35(10):9447-57.; Peters AL, Stunz LL, Bishop GA. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol. 2009 Oct;21(5):293-300.). Consistent with its widespread expression on normal cells, CD40 is also present on the membranes of a wide range of malignant cells, including non-Hodgkin and Hodgkin lymphomas, myelomas, and certain types of carcinomas, including those of the nasopharynx, bladder, cervix, kidney, and ovary (Elgueta R, Benson MJ, de Vries VC, et al. Molecular mechanism and function of CD40 / CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72.; Eliopoulos AG, Young LS. The role of the CD40 pathway in the pathogenesis and treatment of cancer. Curr Opin Pharmacol. 2004 Aug;4(4):360-7). CD40 interacts with a single ligand, CD40L (CD154), a transmembrane protein that is expressed by activated T cells, but also on B cells, platelets, mast cells, macrophages, basophils, natural killer (NK) cells, and non-hematopoietic cells (smooth muscle cells, endothelial cells, and epithelial cells) (Elgueta R, Benson MJ, de Vries VC, et al. Molecular mechanism and function of CD40 / CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72.; Korniluk A, Kemona H, Dymicka-Piekarska V. Multifunctional CD40L: pro- and anti-neoplastic activity. Tumour Biol. 2014 Oct;35(10):9447-57). The binding of CD40 to CD40L, as part of a cell-cell interaction, activates an intracellular signal transduction pathway that involves a series of adapter molecules known as TNFR activation factors (TRAF). To initiate this intracellular signal transduction, multiple CD40 receptor trimers must form a higher order cluster on the cell membrane (Peters AL, Stunz LL, Bishop GA. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol. 2009 Oct;21(5):293-300; Werneburg BG, Zoog SJ, Dang TT, et al. Molecular characterization of CD40 signaling intermediates. J Biol Chem. 2001 Nov 16;276(46):43334-42). The CD40 clustering forms a signaling complex that allows multiple TRAF to assemble, which in turn leads to the activation of downstream transcription factors, including NFljB (Elgueta R, Benson MJ, de Vries VC, et al. Molecular mechanism and function of CD40 / CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72; Kornbluth RS, Stempniak M, Stone GW. Design of CD40 agonists and their use in growing B cells for cancer immunotherapy. Int Rev Immunol. 2012 Aug;31(4):279-88). The molecular consequences of CD40 signaling depend on the cell type expressing CD40 and their microenvironment (Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013 Mar 01;19(5):1035-43). The ‘licensing’ of APC, in particular DC, results in up-regulation of membrane co-stimulatory molecules and MHC, as well as the production of pro-inflammatory cytokines (Caux C, Massacrier C, Vanbervliet B, et al. Activation of human dendritic cells through CD40 cross-linking. J Exp Med. 1994 Oct 1;180(4):1263-72; van Kooten C, Banchereau J. Functions of CD40 on B cells, dendritic cells and other cells. Curr Opin Immunol. 1997 Jun;9(3):330-7). Thus, CD40 is involved in the functional maturation of APC and consequently the activation of antigen-specific T cells (Ma DY, Clark EA. The role of CD40 and CD154 / CD40L in dendritic cells. Semin Immunol. 2009 Oct;21(5):265-72; Moran AE, Kovacsovics-Bankowski M, Weinberg AD. The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy. Curr Opin Immunol. 2013 Apr;25(2):230- 7). CD40 also plays a role in humoral immunity by activating resting B cells and by increasing their antigen-presenting function (Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013 Mar 01;19(5):1035-43; Zarnegar B, He JQ, Oganesyan G, et al. Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8108-13). Moreover, CD40 is involved in the induction of innate immunity through stimulation of cells such as macrophages, granulocytes and NK cells (Rakhmilevich AL, Alderson KL, Sondel PM. T-cell- independent antitumor effects of CD40 ligation. Int Rev Immunol. 2012 Aug;31(4):267-78). Monoclonal CD40 agonist antibodies are believed to trigger anti-tumor effects via two distinct mechanisms: (i) tumor-specific immune activation; and (ii) direct tumoricidal effects via e.g., apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and / or complement-dependent cytotoxicity (CDC) (Khong A, Nelson DJ, Nowak AK, et al. The use of agonistic anti-CD40 therapy in treatments for cancer. Int Rev Immunol. 2012 Aug;31(4):246-66). Treatment with CD40 agonists induces activation of several different immune cells that contribute to the anti-tumor immune response. T cells, and in particular cytotoxic T lymphocytes (CTL), are essential for the anti-tumor effects induced by CD40 agonists, as demonstrated in a range of preclinical models (Byrne KT, Vonderheide RH. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer. Cell Rep. 2016 Jun 21;15(12):2719-32; Mangsbo SM, Broos S, Fletcher E, et al. The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T-cell-dependent tumor immunity. Clin Cancer Res. 2015 Mar 01;21(5):1115-26; Tutt AL, O'Brien L, Hussain A, et al. T Cell Immunity to Lymphoma Following Treatment with Anti-CD40 Monoclonal Antibody. The Journal of Immunology. 2002;168(6):2720-2728; van Mierlo GJ, den Boer AT, Medema JP, et al. CD40 stimulation leads to effective therapy of CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte immunity. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5561-6). Activation of DC and subsequent priming of T cells likely plays a central role, as the presence of antigen cross-presenting DC is required for the anti- tumor effects of CD40 agonist treatment in T cell-dependent models (Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011 Mar 25;331(6024):1612-6; Beatty GL, Li Y, Long KB. Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists. Expert Rev Anticancer Ther. 2017 Feb;17(2):175-186; Long KB, Gladney WL, Tooker GM, et al. IFNgamma and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. Cancer Discov. 2016 Apr;6(4):400-413; Lum HD, Buhtoiarov IN, Schmidt BE, et al. In vivo CD40 ligation can induce T-cell-independent antitumor effects that involve macrophages. J Leukoc Biol. 2006 Jun;79(6):1181-92). NK cells are also capable of cytotoxic killing of tumor cells, and have been shown to contribute to the reduction in tumor growth in response to a CD40 agonist (Turner JG, Rakhmilevich AL, Burdelya L, et al. Anti-CD40 Antibody Induces Antitumor and Antimetastatic Effects: The Role of NK Cells. The Journal of Immunology. 2001;166(1):89). B cells activated through CD40 can further add to the anti-tumor immune response by presenting antigen to T cells and producing tumor- targeting antibodies (Jackaman C, Cornwall S, Graham PT, et al. CD40-activated B cells contribute to mesothelioma tumor regression. Immunol Cell Biol. 2011 Feb;89(2):255-67; Liu M, Sun Q, Wang J, et al. A New Perspective: Exploring Future Therapeutic Strategies For Cancer By Understanding The Dual Role Of B Lymphocytes In Tumor Immunity. Int J Cancer. 2018 Sep 5). Additionally, CD40 agonists have been found to convert tumor-associated macrophages (TAM) to activated macrophages with anti-tumor properties that can promote tumor shrinkage, independent of T cells (Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011 Mar 25;331(6024):1612-6; Beatty GL, Li Y, Long KB. Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists. Expert Rev Anticancer Ther. 2017 Feb;17(2):175-186; Long KB, Gladney WL, Tooker GM, et al. IFNgamma and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. Cancer Discov. 2016 Apr;6(4):400-413; Lum HD, Buhtoiarov IN, Schmidt BE, et al. In vivo CD40 ligation can induce T-cell-independent antitumor effects that involve macrophages. J Leukoc Biol. 2006 Jun;79(6):1181-92). DC are the most important APC for the generation of antigen-specific T cell responses (Flamar AL, Xue Y, Zurawski SM, et al. Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells. AIDS. 2013 Aug 24;27(13):2041-51). Their central role in inducing anti-tumor immune responses has been shown in preclinical models, where mice deficient in Batf3 and thereby lacking cross-presenting DC (cDC1), show impaired rejection of immunogenic tumors and fail to respond to immunotherapy due to impaired priming of tumor- targeting CTL (Hildner K, Edelson BT, Purtha WE, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 2008 Nov 14;322(5904):1097-100; Sanchez-Paulete AR, Cueto FJ, Martinez-Lopez M, et al. Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti-PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells. Cancer Discov.2016 Jan;6(1):71-9). In accordance with these data, the presence of cross-presenting DC in human tumors correlates with CD8+ T cell infiltration and is associated with better prognosis as well as better response to immunotherapy (Broz ML, Binnewies M, Boldajipour B, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014 Nov 10;26(5):638-52; Sanchez-Paulete AR, Teijeira A, Cueto FJ, et al. Antigen Cross- Presentation and T-Cell Cross-Priming In Cancer Immunology And Immunotherapy. Ann Oncol. 2017 Sep 01). Signaling through CD40 on DC induces activation of the antigen presentation machinery and upregulation of co-stimulatory molecules such as CD80 and CD86, thereby improving the capacity of the DC to present antigen to and activate T cells (Beatty GL, Li Y, Long KB. Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists. Expert Rev Anticancer Ther. 2017 Feb;17(2):175-186; Gladue RP, Paradis T, Cole SH, et al. The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice. Cancer Immunol Immunother.2011 Jul;60(7):1009-17), and to produce cytokines, notably IL-12, that helps shape the T cell response. CD40 expression can be detected on all blood DC, with the highest expression found on a subpopulation referred to as cDC1 (Carenza C, Calcaterra F, Oriolo F, et al. Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells [Original Research]. Frontiers in Immunology.2019 2019-June-11;10(1325); MacDonald KP, Munster DJ, Clark GJ, et al. Characterization of human blood dendritic cell subsets. Blood. 2002 Dec 15;100(13):4512-20). Recent studies have focused on the role of cDC1 in driving T cell responses to tumors, demonstrating a potential for CD40 agonists alone or in combination with other therapies in enhancing cDC1 priming of tumor-targeting T cells (Hegde S, Krisnawan VE, Herzog BH, et al. Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer. Cancer Cell. 2020 Mar 16;37(3):289-307 e9; Morrison AH, Diamond MS, Hay CA, et al. Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity. Proc Natl Acad Sci U S A. 2020 Mar 25; Zhang L, Li Z, Skrzypczynska KM, et al. Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer. Cell. 2020;181(2):442- 459.e29). Single-cell RNA sequencing studies confirm the presence of cDC1 with the potential to respond to CD40 agonists in primary tumor tissue (Chevrier S, Levine JH, Zanotelli VRT, et al. An Immune Atlas of Clear Cell Renal Cell Carcinoma. Cell. 2017;169(4):736-749.e18; Zhang L, Li Z, Skrzypczynska KM, et al. Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer. Cell. 2020;181(2):442-459.e29; Zhang Q, He Y, Luo N, et al. Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell. 2019;179(4):829-845.e20). Targeting CD40 on DC therefore has the capacity to expand the tumor-specific T cell pool, and potentially represents a way to treat immunologically “cold” tumors. Carcinoembryonic antigen (CEA) Carcinoembryonic antigen (CEA) describes a family of highly-related glycoproteins (some of which are glycosyl phosphatidyl inositol (GPI) cell-surface-anchored), which are involved in cell functions, such as cell adhesion, phagocytosis, proliferation and signal transduction. CEAs are generally characterised as being members of the CD66 family of molecules (with CEA including examples of CD66a, CD66b, CD66c, CD66d, CD66e, and CD66f molecules). Currently 29 CEA family genes have been identified, which are generally referred to as carcinoembryonic antigen-related cell adhesion molecule (CEACAMs). Examples of the CEACAM genes are CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20, and CEACAM21. CEA (and, in particular, CEACAM5) is usually produced during the development of a fetus, and is only present at very low levels in the blood of a healthy, human, adult. However, in cancer the levels of CEA found are increased, and in that context it is characterised as a tumour-associated antigen (TAA). CEA has been associated with many types of cancers and tumours, including gastric carcinoma, pancreatic carcinoma, lung carcinoma, breast carcinoma, and medullary thyroid carcinoma. Of particular relevance to cancer and tumours are CEACAM1, CEACAM6, CEACAM7 and CEACAM5 (Zi-Wen Han, Zhi-Wu Lyv, Bin Cui, et al. The old CEACAMs find their new role in tumor immunotherapy. Invest New Drugs volume.202038:1888–1898; Chaogu Zheng, Jing Feng1, Di Lu1, et al. A Novel Anti-CEACAM5 Monoclonal Antibody, CC4, Suppresses Colorectal Tumor Growth and Enhances NK Cells-Mediated Tumor Immunity. PLoS One. 2011;6(6):e21146). Despite progress in the development of immunotherapies for the treatment of various cancers over the last decade, there remains a need for new and efficacious agents for treating cancers, in particular cancers expressing CEA. Accordingly, the present invention seeks to provide improved polypeptide-based therapies for the treatment of cancer, in particular cancers expressing CEA. PD-1 The programmed death-1 (PD-1) receptor is a negative regulator of anti-tumor T cell effector function when engaged by its ligand PD-L1, expressed on the surface of cells within a tumor (Ribas and Wolchok 2018). The PD-1 is an immune checkpoint, with its inhibitory function mediated by the tyrosine phosphatase SHP-2 that de- phosphorylates signaling molecules downstream of the T cell receptor (TCR) signaling molecules. PD-1 has two ligands, programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1), which is broadly expressed by many somatic cells mainly upon exposure to pro-inflammatory cytokines, and programmed death-ligand 2 (PD-L2, also known as CD273 or B7-DC), which has more restricted expression in antigen- presenting cells. Inflammation-induced PD-L1 expression in the tumor microenvironment results in PD-1-mediated T cell exhaustion, inhibiting the antitumor cytotoxic T cell response. PD-L1 is expressed on both tumor cells and myeloid cells. PD-1 resistance can broadly be subdivided into primary resistance or secondary (acquired) resistance. (Kluger et al. 2020). Summary of the invention Accordingly, the present invention seeks to provide improved polypeptide-based therapies for the treatment of cancer, in particular cancers expressing CEA. The inventors have surprisingly found that a combination therapy comprising a CD40- CEA bispecific antibody or antigen-binding fragments thereof and a PD-1 inhibitor (such as an anti-PD-1 antibody, an anti-PD-L1 antibody or antigen binding fragments thereof) is surprisingly efficacious in the treatment of cancer. As shown herein in the Examples, the combination of a CD40xCEA bispecific antibody and a PD-1 inhibitor (such as an anti-PD-1 antibody or an anti-PD-L1 antibody) surprisingly led to a synergistic effect both in vitro and in vivo compared to use of the CD40xCEA bispecific or PD-1 inhibitor alone. The inventors also show herein that this effect is supported by the finding that the CD40xCEA bispecific antibody induces upregulation of PD-1 and PD-L1 expression. Such an effect could not have been predicted prior to the present invention. In a first aspect, the invention provides a combination therapy comprising (a) bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to CEA, and (b) a PD-1 inhibitor, wherein the PD-1 inhibitor is formulated for parenteral delivery. A second aspect of the invention provides a pharmaceutical composition comprising an effective amount of (a) a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) a PD-1 inhibitor, wherein the PD-1 inhibitor is formulated for parenteral delivery. Such combination therapies and pharmaceutical compositions can be used to establish a highly effective and safe cancer immunotherapy. A third aspect of the invention provides the combination therapies or pharmaceutical compositions for use in medicine. In particular, for use in the treatment of cancer and / or a tumour in a subject. Preferably wherein the tumour is a solid tumour. A fourth aspect of the invention provides use of the combination therapy or the pharmaceutical composition in the preparation of a medicament. Preferably wherein the medicament is for treating cancer and / or a tumour as described herein. A fifth aspect of the invention provides a method for the treatment of cancer and / or a tumour in a subject, comprising (a) administering to the subject an effective amount of a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) administering to the subject an effective amount of a PD-1 inhibitor, wherein the PD-1 inhibitor is administered parenterally. A sixth aspect of the invention provides a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA) for use in medicine, wherein the bispecific polypeptide is for use in combination with a PD-1 inhibitor and wherein the PD-1 inhibitor is formulated for parenteral administration. A seventh aspect of the invention provides a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA) for use in the treatment of a cancer and / or a tumour in a subject, wherein the bispecific polypeptide is for use in combination with a PD-1 inhibitor and wherein the PD-1 inhibitor is formulated for parenteral administration. An eighth aspect of the invention includes a combination therapy, pharmaceutical composition, bispecific polypeptide, method or use substantially as described herein with reference to the description and figures. The clinical progress with immunocytokines has so far not been impressive and the side effects still remain since the tumor-binding entity only confers limited tumor localization, with the bulk of the immunocytokine ending up in other compartments. Bispecific antibodies that restrict the activity to the tumor as described in the combination therapy and pharmaceutical compositions of the invention would provide a clear advantage over immunocytokines since they are inactive in the absence of cancer and / or tumours, in particular cancer and / or tumours that express CEA. To avoid affecting part of the immune system not relevant for inducing tumour immunity and avoid systemic toxicity by CD40-activating agents, yet obtain high efficacy in the tumour area, the designs of the molecular formats of CD40 agonists may be optimised. For example, a good efficacy / safety profile can be obtained by a CD40-CEA bispecific antibody that requires crosslinking by binding to the CEA for CD40 activation to occur. Thus, CD40-expressing cells such as dendritic cells, residing in the tumour tissue, will preferentially be activated, whereas CD40-expressing cells in other tissues, where the expression of CEA is low or absent, will not. This would allow focused activation of CD40-expressing cells specifically in the tumour tissue, while limiting toxicity induced by generalised CD40 activation. Detailed description of the invention Structure of the bispecific polypeptide of the combination therapy or pharmaceutical composition A “polypeptide” is used herein in its broadest sense to refer to a compound of two or more subunit amino acids, amino acid analogs, or other peptidomimetics. The term “polypeptide” thus includes short peptide sequences and also longer polypeptides and proteins. As used herein, the term “amino acid” refers to either natural and / or unnatural or synthetic amino acids, including both D or L optical isomers, and amino acid analogs and peptidomimetics. The term “bispecific” as used herein means the polypeptide is capable of specifically binding at least two target entities. Accordingly, bispecific as used herein can describe polypeptides that are capable of specifically binding more than two target entities, such as: at least three, at least four or at least five target entities. In a preferred embodiment, the bispecific polypeptide is capable of specifically binding two target entities. Thus, the first and / or second binding domains may be selected from the group consisting of antibodies and antigen-binding fragments thereof, and CD40 ligands. By “an antibody or an antigen-binding fragment thereof” we include substantially intact antibody molecules, as well as chimeric antibodies, humanised antibodies, isolated human antibodies, single chain antibodies, bispecific antibodies, antibody heavy chains, antibody light chains, homodimers and heterodimers of antibody heavy and / or light chains, and antigen-binding fragments and derivatives of the same. Suitable antigen-binding fragments and derivatives include Fv fragments (e.g. single chain Fv and disulphide-bonded Fv), Fab-like fragments (e.g. Fab fragments, Fab’ fragments and F(ab)2 fragments), single variable domains (e.g. VH and VL domains) and single domain antibodies (dAbs, including single and dual formats [i.e. dAb-linker-dAb], and nanobodies). The potential advantages of using antibody fragments, rather than whole antibodies, are several-fold. The smaller size of the fragments may lead to improved pharmacological properties, such as better penetration of solid tissue. Moreover, antigen-binding fragments such as Fab, Fv, ScFv and dAb antibody fragments can be expressed in and secreted from E. coli, thus allowing the facile production of large amounts of the said fragments. In one preferred embodiment, the polypeptide is a bispecific antibody (numerous examples of which are described in detail below). In one embodiment, the antigen-binding fragment is selected from the group consisting of: Fv fragments (such as a single chain Fv fragment, or a disulphide-bonded Fv fragment), Fab-like fragments (such as a Fab fragment; a Fab’ fragment or a F(ab)2fragment) and single domain antibodies. The phrase “an antibody or an antigen-binding fragment thereof” is also intended to encompass antibody mimics (for example, non-antibody scaffold structures that have a high degree of stability yet allow variability to be introduced at certain positions). Those skilled in the art of biochemistry will be familiar with many such molecules, as discussed in Gebauer & Skerra, 2009 (the disclosures of which are incorporated herein by reference). Exemplary antibody mimics include: affibodies (also called Trinectins; Nygren, 2008, FEBS J, 275, 2668-2676); CTLDs (also called Tetranectins; Innovations Pharmac. Technol. (2006), 27-30); adnectins (also called monobodies; Meth. Mol. Biol., 352 (2007), 95-109); anticalins (Drug Discovery Today (2005), 10, 23-33); DARPins (ankyrins; Nat. Biotechnol. (2004), 22, 575-582); avimers (Nat. Biotechnol. (2005), 23, 1556-1561); microbodies (FEBS J, (2007), 274, 86-95); peptide aptamers (Expert. Opin. Biol. Ther. (2005), 5, 783-797); Kunitz domains (J. Pharmacol. Exp. Ther. (2006) 318, 803-809); affilins (Trends. Biotechnol. (2005), 23, 514-522); affimers (Avacta Life Sciences, Wetherby, UK). Also included within the scope of the bispecific polypeptide are chimeric T cell receptors (also known as chimeric immunoreceptors, and chimeric antigen receptors or CARs) (see Pule et al., 2003, the disclosures of which are incorporated herein by reference). These are engineered receptors, which graft an arbitrary specificity onto an immune effector cell. Typically, CARs are used to graft the specificity of a monoclonal antibody onto a T cell; with transfer of their coding sequence facilitated by retroviral vectors. The most common form of such molecules is fusions comprising a single-chain variable fragment (scFv) derived from a monoclonal antibody fused to CD3-zeta transmembrane and endodomain. When T cells express this fusion molecule, they recognize and kill target cells that express the transferred monoclonal antibody specificity. Persons skilled in the art will further appreciate that the bispecific polypeptide also encompasses modified versions of antibodies and antigen-binding fragments thereof, whether existing now or in the future, e.g. modified by the covalent attachment of polyethylene glycol or another suitable polymer (see below). Methods of generating antibodies and antibody fragments are well known in the art. For example, antibodies may be generated via any one of several methods which employ induction of in vivo production of antibody molecules, screening of immunoglobulin libraries (Orlandi. et al, 1989; Winter et al., 1991, the disclosures of which are incorporated herein by reference) or generation of monoclonal antibody molecules by cell lines in culture. These include, but are not limited to, the hybridoma technique, the human B cell hybridoma technique, and the Epstein-Barr virus (EBV)- hybridoma technique (Kohler et al., 1975, Kozbor et al., 1985; Cote et al., 1983; Cole et al., 1984., the disclosures of which are incorporated herein by reference). Suitable methods for the production of monoclonal antibodies are also disclosed in “Monoclonal Antibodies: A manual of techniques”, H Zola (CRC Press, 1988, the disclosures of which are incorporated herein by reference) and in “Monoclonal Hybridoma Antibodies: Techniques and Applications”, J G R Hurrell (CRC Press, 1982, the disclosures of which are incorporated herein by reference). Likewise, antibody fragments can be obtained using methods well known in the art (see, for example, Harlow & Lane, 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory, New York, the disclosures of which are incorporated herein by reference). For example, antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster ovary cell culture or other protein expression systems) of DNA encoding the fragment. Alternatively, antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. It will be appreciated by persons skilled in the art that for human therapy or diagnostics, human or humanised antibodies are preferably used. Humanised forms of non-human (e.g. murine) antibodies are genetically engineered chimeric antibodies or antibody fragments having preferably minimal-portions derived from non-human antibodies. Humanised antibodies include antibodies in which complementary determining regions of a human antibody (recipient antibody) are replaced by residues from a complementary determining region of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired functionality. In some instances, Fv framework residues of the human antibody are replaced by corresponding non-human residues. Humanised antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported complementarity determining region or framework sequences. In general, the humanised antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the complementarity determining regions correspond to those of a non-human antibody and all, or substantially all, of the framework regions correspond to those of a relevant human consensus sequence. Humanised antibodies optimally also include at least a portion of an antibody constant region, such as an Fc region, typically derived from a human antibody (see, for example, Jones et al., 1986, Riechmann et al., 1988, Presta, 1992, the disclosures of which are incorporated herein by reference). Methods for humanising non-human antibodies are well known in the art. Generally, the humanised antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues, often referred to as imported residues, are typically taken from an imported variable domain. Humanisation can be essentially performed as described (see, for example, Jones et al., 1986, Reichmann et al., 1988, Verhoeyen et al., 1988, US 4,816,567, the disclosures of which are incorporated herein by reference) by substituting human complementarity determining regions with corresponding rodent complementarity determining regions. Accordingly, such humanised antibodies are chimeric antibodies, wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanised antibodies may be typically human antibodies in which some complementarity determining region residues and possibly some framework residues are substituted by residues from analogous sites in rodent antibodies. Human antibodies can also be identified using various techniques known in the art, including phage display libraries (see, for example, Hoogenboom & Winter, 1991, Marks et al., 1991, Cole et al., 1985, Boerner et al., 1991, the disclosures of which are incorporated herein by reference). It will be appreciated by persons skilled in the art that the bispecific polypeptides, e.g. antibodies, may be of any suitable structural format. Thus, in exemplary embodiments of the bispecific antibodies: (a) binding domain B1 and / or binding domain B2 is an intact IgG antibody (or, together, form an intact IgG antibody); (b) binding domain B1 and / or binding domain B2 is an Fv fragment (e.g. an scFv); (c) binding domain B1 and / or binding domain B2 is a Fab fragment; and / or (d) binding domain B1 and / or binding domain B2 is a single domain antibody (e.g. domain antibodies and nanobodies). It will be appreciated by persons skilled in the art that the bispecific antibody may comprise a human Fc region, or a variant of a said region, where the region is an IgG1, IgG2, IgG3 or IgG4 region, preferably an IgG1 or IgG4 region. Engineering the Fc region of a therapeutic monoclonal antibody or Fc fusion protein allows the generation of molecules that are better suited to the pharmacology activity required of them (Strohl, 2009, the disclosures of which are incorporated herein by reference). By “CD40 ligands”, we include non-antibody molecules that are capable of binding to CD40; for example CD40L (CD154, such as GenBank: D31797.2) or fragments or variants of CD40L that retain their ability to bind to CD40. (a) Engineered Fc regions for increased half-life One approach to improve the efficacy of a therapeutic antibody is to increase its serum persistence, thereby allowing higher circulating levels, less frequent administration and reduced doses. The half-life of an IgG depends on its pH-dependent binding to the neonatal receptor FcRn. FcRn, which is expressed on the surface of endothelial cells, binds the IgG in a pH-dependent manner and protects it from degradation. Some antibodies that selectively bind the FcRn at pH 6.0, but not pH 7.4, exhibit a higher (to put another way longer) half-life in a variety of animal models. Additionally, some antibodies that bind the FcRn with a higher affinity at pH 6.0, but with a remained low affinity at pH 7.4 exhibit a longer half-life. Several mutations located at the interface between the CH2 and CH3 domains, such as T250Q / M428L (Hinton et al., 2004, the disclosures of which are incorporated herein by reference) and M252Y / S254T / T256E + H433K / N434F (Vaccaro et al., 2005, the disclosures of which are incorporated herein by reference), have been shown to increase the binding affinity to FcRn and the half-life of IgG1 in vivo. (b) Engineered Fc regions for altered effector function To ensure lack of CD40 activation in the absence of CEA, the Fc portion of the bispecific antibody should bind with no or very low affinity to FcDŽR, since FcDŽR-mediated crosslinking of a CD40 antibody may induce activation. By “very low affinity” we include that the Fc portion exhibits at least 10 times reduced affinity to FcDŽRI, FcDŽRII and III compared to wild-type IgG1, as determined by the concentration where half maximal binding is achieved in flow cytometric analysis of FcDŽR expressing cells (Hezareh et al., 2001) or by FcDŽR ELISA (Shields et al., 2001). Another factor to take into account is that engagement of FcDŽRs may also induce antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC) of cells coated with antibodies. In one embodiment, to enhance tumour-dependent CD40 activation as well as to avoid depletion of CD40-expressing cells, the isotype of a CD40-CEA bispecific antibody should preferably be silent. The four human IgG isotypes bind the activating FcDŽ receptors (FcDŽRI, FcDŽRIIa, FcDŽRIIIa), the inhibitory FcDŽRIIb receptor, and the first component of complement (C1q) with different affinities, yielding very different effector functions (Bruhns et al., 2009, the disclosures of which are incorporated herein by reference). IgG1 molecules have the highest affinity and capacity to induce effector functions, whereas IgG2, IgG3 and IgG4 are less effective (Bruhns, 2012; Hogarth and Pietersz, 2012; Stewart et al., 2014) (Wang et al. 2015; Vidarson et al. 2014). In addition, certain mutations in the Fc region of IgG1 dramatically reduce FcDŽR affinity and effector function while retaining neonatal FcR (FcRn) interaction (Ju and Jung, 2014; Leabman et al., 2013; Oganesyan et al., 2008; Sazinsky et al., 2008). The most widely used IgG1 mutants are N297A alone or in combination with D265A, as well as mutations at positions L234 and L235, including the so-called “LALA” double mutant L234A / L235A. Another position described to further silence IgG1 by mutation is P329 (see US 2012 / 0251531). Thus, choosing a mutated IgG1 format with low effector function but retained binding to FcRn may result in a bispecific antibody with CEA-dependent activation of CD40, and exhibiting a favorable efficacy / safety profile and good PK properties. Advantageously, the polypeptide is incapable of inducing antibody-dependent cell cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and / or complement-dependent cytotoxicity (CDC). By “incapable” we include that the ability of the polypeptide to induce ADCC, etc., is at least 10-fold lower than compared to wild-type IgG1 as shown by e.g. monocyte-dependent ADCC or CDC assays described by Hezareh et al. 2001. In one embodiment, the Fc region may be a variant of a human IgG1 Fc region comprising a mutation at one or more of the following positions: L234, L235, P239, D265, N297 and / or P329. Advantageously, alanine may be present at the mutated position(s). Optionally, the IgG1 variant may be a variant of a human IgG1 Fc region comprising mutations L234A and L235A (i.e. the LALA double mutant; see SEQ ID NO: 336). It will be appreciated by persons skilled in the art that the bispecific polypeptides may be of several different structural formats (for example, see Chan & Carter, 2016, the disclosures of which are incorporated herein by reference). In exemplary embodiments, the bispecific antibody is selected from the groups consisting of: (a) bivalent bispecific antibodies, such as IgG-scFv bispecific antibodies (for example, wherein B1 is an intact IgG and B2 is an scFv attached to B1 at the N- terminus of a light chain and / or at the C-terminus of a light chain and / or at the N- terminus of a heavy chain and / or at the C-terminus of a heavy chain of the IgG, or vice versa); (b) monovalent bispecific antibodies, such as a DuoBody®(Genmab AS, Copenhagen, Denmark) or ‘knob-in-hole’ bispecific antibody (for example, an scFv- KIH, scFv-KIHr, a BiTE-KIH or a BiTE-KIHr(see Xu et al., 2015, mAbs 7(1):231-242)); (c) scFv2-Fc bispecific antibodies (such as ADAPTIR™ bispecific antibodies from Aptevo Therapeutics); (d) BiTE / scFv2bispecific antibodies; (e) DVD-Ig bispecific antibodies; (f) DART-based bispecific antibodies (for example, DART2-Fc or DART); (g) DNL-Fab3bispecific antibodies; and (h) scFv-HSA-scFv bispecific antibodies. For example, the bispecific antibody may be an IgG-scFv antibody. The IgG-scFv antibody may be in either VH-VL or VL-VH orientation. In one embodiment, the scFv may be stabilised by a S-S bridge between VH and VL. In one embodiment, binding domain B1 and binding domain B2 are fused directly to each other. In an alternative embodiment, binding domain B1 and binding domain B2 are joined via a polypeptide linker. For example, a polypeptide linker may be a short linker peptide between about 10 to about 25 amino acids. The linker is usually rich in glycine for flexibility, as well as serine or threonine for solubility, and can either connect the N-terminus of the VH with the C-terminus of the VL, or vice versa. Thus, the linker may be selected from the group consisting of the amino acid sequence SGGGGSGGGGS (SEQ ID NO: 337), SGGGGSGGGGSAP (SEQ ID NO: 338), NFSQP (SEQ ID NO: 339), KRTVA (SEQ ID NO: 340), GGGSGGGG (SEQ ID NO: 341), GGGGSGGGGS, (SEQ ID NO: 342), GGGGSGGGGSGGGGS (SEQ ID NO: 343), GSTSGSGKPGSGEGSTKG (SEQ ID NO: 344) (Whitlow et al. 1993) THTCPPCPEPKSSDK (SEQ ID NO: 345), GGGS (SEQ ID NO: 346), EAAKEAAKGGGGS (SEQ ID NO: 347), EAAKEAAK (SEQ ID NO: 348), or (SG)m, where m = 1 to 7. In a preferred embodiment, the linker may be selected from the group consisting of: SEQ ID NO: 341, SEQ ID NO: 342 and SEQ ID NO: 343. In a particularly preferred embodiment, the linker is GGGGSGGGGSGGGGS (SEQ ID NO: 343). The term “amino acid” as used herein includes the standard twenty genetically- encoded amino acids and their corresponding stereoisomers in the ‘D’ form (as compared to the natural ‘L’ form), omega-amino acids other naturally-occurring amino acids, unconventional amino acids (e.g. Į,Į-disubstituted amino acids, N-alkyl amino acids, etc.) and chemically derivatised amino acids (see below). When an amino acid is being specifically enumerated, such as “alanine” or “Ala” or “A”, the term refers to both L-alanine and D-alanine unless explicitly stated otherwise. Other unconventional amino acids may also be suitable components for the bispecific polypeptides, as long as the desired functional property is retained by the polypeptide. For the peptides shown, each encoded amino acid residue, where appropriate, is represented by a single letter designation, corresponding to the trivial name of the conventional amino acid. In one embodiment, the bispecific polypeptides comprise or consist of L-amino acids. It will be appreciated by persons skilled in the art that the bispecific polypeptides may comprise or consist of one or more amino acids which have been modified or derivatised. Chemical derivatives of one or more amino acids may be achieved by reaction with a functional side group. Such derivatised molecules include, for example, those molecules in which free amino groups have been derivatised to form amine hydrochlorides, p-toluene sulphonyl groups, carboxybenzoxy groups, t- butyloxycarbonyl groups, chloroacetyl groups or formyl groups. Free carboxyl groups may be derivatised to form salts, methyl and ethyl esters or other types of esters and hydrazides. Free hydroxyl groups may be derivatised to form O-acyl or O-alkyl derivatives. Also included as chemical derivatives are those peptides which contain naturally occurring amino acid derivatives of the twenty standard amino acids. For example: 4-hydroxyproline may be substituted for proline; 5-hydroxylysine may be substituted for lysine; 3-methylhistidine may be substituted for histidine; homoserine may be substituted for serine and ornithine for lysine. Derivatives also include peptides containing one or more additions or deletions as long as the requisite activity is maintained. Other included modifications are amidation, amino terminal acylation (e.g. acetylation or thioglycolic acid amidation), terminal carboxylamidation (e.g. with ammonia or methylamine), and the like terminal modifications. It will be further appreciated by persons skilled in the art that peptidomimetic compounds may also be useful. The term ‘peptidomimetic’ refers to a compound that mimics the conformation and desirable features of a particular peptide as a therapeutic agent. For example, the said polypeptide includes not only molecules in which amino acid residues are joined by peptide (-CO-NH-) linkages but also molecules in which the peptide bond is reversed. Such retro-inverso peptidomimetics may be made using methods known in the art, for example such as those described in Meziere et al. (1997), which is incorporated herein by reference. This approach involves making pseudo- peptides containing changes involving the backbone, and not the orientation of side chains. Retro-inverse peptides, which contain NH-CO bonds instead of CO-NH peptide bonds, are much more resistant to proteolysis. Alternatively, the said polypeptide may be a peptidomimetic compound wherein one or more of the amino acid residues are linked by a -y(CH2NH)- bond in place of the conventional amide linkage. In a further alternative, the peptide bond may be dispensed with altogether provided that an appropriate linker moiety which retains the spacing between the carbon atoms of the amino acid residues is used; it may be advantageous for the linker moiety to have substantially the same charge distribution and substantially the same planarity as a peptide bond. It will also be appreciated that the said polypeptide may conveniently be blocked at its N- or C-terminus so as to help reduce susceptibility to exo-proteolytic digestion. A variety of un-coded or modified amino acids such as D-amino acids and N-methyl amino acids have also been used to modify mammalian peptides. In addition, a presumed bioactive conformation may be stabilised by a covalent modification, such as cyclisation or by incorporation of lactam or other types of bridges, for example see Veber et al., 1978 and Thursell et al., 1983, which are incorporated herein by reference. In one embodiment, one of binding domain B1 or binding domain B2 is an immunoglobulin molecule, and one of binding domain B1 or binding domain B2 is a Fab fragment, wherein the Fab fragment is fused to the C terminus of the heavy chain of the immunoglobulin via the light chain of the Fab fragment. For example, the polypeptide may have a format as shown in Figure 23. Such a format is referred to as the “RUBY™ format” (as described in pending UK patent application 1820556.7 and the PCT application WO 2020 / 127354). Antibodies in the “RUBY™ format” and “optimised RUBY™ format”, as described herein, are particularly preferred, for the bispecific polypeptides. The bispecific polypeptide may comprise one or more mutations to promote association of the heavy chain polypeptide of the immunoglobulin with the light chain polypeptide of the immunoglobulin and / or to promote association of the heavy chain polypeptide of the Fab with the light chain polypeptide of the Fab. In one embodiment the one or more mutations prevent the formation of aggregates and a Fab by-product. It will be appreciated by persons skilled in the art, that in one embodiment the mutations may prevent the formation of aggregates and / or a Fab by-product by generating steric hindrance and / or incompatibility between charges. By “steric hindrance” we mean the slowing of a reaction due to steric bulk, i.e. the size of an amino acid molecule prevents association of two protein surfaces that may otherwise occur if a smaller amino acid is present. By “incompatibility between charges” we mean that an unwanted product will not form as the charges are incompatible and prevent the product from forming, e.g. there may be two negatively charged portions which repel and prevent an unwanted product from forming. As described above, said mutations limit the formation of a Fab by-product and / or aggregates by, for example, creating surfaces that limit the formation of aggregates or by-product Fab fragments. In one embodiment, the mutations prevent formation of a Fab by-product by generating steric hindrance and / or incompatibility between charges (leading to charge incompatibility of wrong chains). The mutations may also promote interactions between correct chains (i.e. between the first heavy chain polypeptide and the first light chain polypeptide, and / or between the second heavy chain polypeptide and the second light chain polypeptide) by, for example, creating salt or disulphide bridges. Thus, the mutations may favour formation of the bispecific polypeptide. In one embodiment, the percentage of aggregates formed during manufacturing is less than or equal to 25%. Optionally the percentage of aggregates is less than or equal to 20%, 17.5%, 15%, 13.5% or 10%. Preferably the percentage of aggregates is less than 10%. Optionally these measurements are carried out when the chains of the bispecific polypeptide are transfected at equal ratios, e.g. at a ratio of 1:1:1 when 3 chains are used during production. Alternatively, the chain transfection ratio may be optimised. Optionally the % of aggregates when the chain transfection ratio is optimised may be less than or equal to 3.5%, 3%, 2.5% or 2%. In one embodiment, the bispecific polypeptide comprises one or more mutation pairs each comprising two functionally compatible mutations. By “functionally compatible mutations” we mean the mutations have complementary functions, e.g. one mutation of the pair (in one chain) may be a mutation that forms a positively charged region, and the other mutation (in another chain) forms a negatively charged region. Together these mutations act in a functionally compatible way promoting association of the respective chains. In one embodiment, the bispecific polypeptide comprises one or more mutation pairs in one or more of the following region groups: (a) the CH1 and CKappa or CLambda region of the immunoglobulin; and / or (b) the CH1 and CKappa or CLambda region of the Fab; and / or (c) the VL and VH regions of the immunoglobulin; and / or (d) the VL and VH regions of the Fab. Thus, in one embodiment, the mutation pairs are in the CH1 and CKappa or CLambda regions of the Fab and / or the immunoglobulin, and the mutation pairs are selected from: (a) cavity and protruding surface mutations (i.e. steric mutations); and / or (b) hydrophobic swap mutations; and / or (c) charged mutations (i.e. salt mutations); and / or (d) mutations resulting in the formation of a disulphide bridge. The mutation pairs may alternatively or additionally be in the VH and VL regions of the Fab and / or the immunoglobulin, the mutation pairs in the VH and VL regions are selected from: (a) charged mutations (i.e. salt mutations); and / or (b) double charged mutations; and / or (c) mutations resulting in the formation of a disulphide bridge. In one embodiment of the bispecific polypeptide comprises mutations at positions selected from the group consisting of: (a) one or more of the following positions in the CH1 domain: H168, F170, L145, S183 and T187 (according to EU numbering system); and / or (b) a position selected from the one or more of the following position ranges in the CKappa or CLambda domain: position 132 to 138, position 173 to 179, position 130 to 136, position 111 to 117 and position 134 to 140 (according to EU numbering system); and / or (c) a position selected from one or more of the following position ranges in the VL: position 41 to 47, position 117 to 123 and position 46 to 52 (according to IMGT numbering system); and / or (d) a position selected from one or more of the following position ranges in the VH: position 41 to 47, position 46 to 52 and position 117 to 123 (according to IMGT numbering system). In one embodiment the bispecific polypeptide comprises mutations at positions selected from the group consisting of: (a) one or more of the following positions in the CH1 domain: H168, F170, L145, S183 and T187 (according to EU numbering system); and / or (b) a position selected from the one or more of the following position ranges in the CKappa or CLambda domain: position 132 to 138, position 173 to 179, position 130 to 136, position 111 to 117 and position 134 to 140 (according to Kabat numbering system); and / or (c) a position selected from one or more of the following position ranges in the VL: position 41 to 47, position 117 to 123 and position 46 to 52 (according to IMGT numbering system); and / or (d) a position selected from one or more of the following position ranges in the VH: position 41 to 47, position 46 to 52 and position 117 to 123 (according to IMGT numbering system). In one embodiment the bispecific polypeptide comprises mutations at positions selected from the group consisting of: (a) one or more of the following positions in the CH1 domain: H168, F170, L145, S183 and T187 (according to EU numbering system); and / or (b) a position selected from the one or more of the following position ranges in the CKappa or CLambda domain: position 132 to 138, position 173 to 179, position 130 to 136, position 111 to 117 and position 134 to 140 (according to EU numbering system); and / or (c) a position selected from one or more of the following position ranges in the VL: position 41 to 47, position 117 to 123 and position 46 to 52 (according to IMGT numbering system); and / or (d) a position selected from one or more of the following position ranges in the VH: position 41 to 47, position 46 to 52 and position 117 to 123 (according to IMGT numbering system). One mutation in each of the ranges given above will be the relevant functional mutation as it will be a position that makes contact with the amino acid in the corresponding domain / chain, and is therefore the relevant interface between chains. It will therefore be appreciated by persons skilled in the art that mutations in the position ranges given above are suitable, as the relevant functional feature is whether the position contacts a corresponding position on the other chain, i.e. a position in the VH chain that contacts a corresponding position in a VL chain is the relevant position, or a position in a CLambda that contacts a position in a CH1 chain is the relevant position. In one embodiment the mutations are selected from the group consisting of: VH X44R / E / D / K, X49C, X120K VL X44R / E / D / K, X49D X120C CH1 H168A / G, F170G / A, L145Q, S183V, T187E / D, CKappa / CLambda S / T114A, V133T, L135Y / W, N / S137K / R / H, S176W / V / Y *numbering according to IMGT system for VH / VL domains and according to EU numbering system for constant domains *X refers to any amino acid The use of “ / ” in the context of discussing mutations is to illustrate alternative possible amino acids; for example, “X44R / E / D / K” indicates that R or E or D or K can be included at position 44, as a substitute for the amino acid “X”. In one embodiment the mutations are selected from the group consisting of: VH X44R / E / D / K, X49C, X120K VL X44R / E / D / K, X49D X120C CH1 H168A / G, F170G / A, L145Q, S183V, T187E / D, CKappa / CLambda S / T114A, V133T, L135Y / W, N / S137K / R / H, S176W / V / Y *numbering according to IMGT system for VH / VL domains and according to Kabat numbering system for constant domains *X refers to any amino acid In one embodiment, the bispecific polypeptide comprises mutations at positions selected from the group consisting of: (a) one or more of the following positions in the CH1 domain: H168, F170, L145, S183 and T187 (according to EU numbering system); and / or (b) one or more of the following positions in the CKappa domain: L135, S176, V133, S114 and N137 (according to EU numbering system) and / or one or more of the following positions in the CLambda domain: L135, S176, V133, T114 and S137 (according to EU numbering system); and / or (c) one or more of the following positions in the VL: Q44, Q120 and A49 (according to IMGT numbering system); and / or (d) one or more of the following positions in the VH: Q44, G49 and Q120 (according to IMGT numbering system). In one embodiment, the bispecific polypeptide comprises mutations at positions selected from the group consisting of: (a) one or more of the following positions in the CH1 domain: H168, F170, L145, S183 and T187 (according to EU numbering system); and / or (b) one or more of the following positions in the CKappa domain: L135, S176, V133, S114 and N137 (according to Kabat numbering system) and / or one or more of the following positions in the CLambda domain: L135, S176, V133, T114 and S137 (according to Kabat numbering system); and / or (c) one or more of the following positions in the VL: Q44, Q120 and A49 (according to IMGT numbering system); and / or (d) one or more of the following positions in the VH: Q44, G49 and Q120 (according to IMGT numbering system). For example, the mutations may be selected from the group consisting of: (a) one or more of the following mutations in the CH1 domain: H168A, F170G, L145Q, S183V and T187E (according to EU numbering system); and / or (b) one or more of the following mutations in the CKappa domain: L135Y, S176W, V133T, S176V, S114A and N137K (according to EU numbering system) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, V133T, S176V, T114A and S137K (according to EU numbering system); and / or (c) one or more of the following mutations in the VL: Q44R, Q44E, Q120C, Q44D and A49D (according to IMGT numbering system); and / or (d) one or more of the following mutations in the VH: Q44E, Q44R, G49C, Q44K and Q120K (according to IMGT numbering system). For example, the mutations may be selected from the group consisting of: (a) one or more of the following mutations in the CH1 domain: H168A, F170G, L145Q, S183V and T187E (according to EU numbering system); and / or (b) one or more of the following mutations in the CKappa domain: L135Y, S176W, V133T, S176V, S114A and N137K (according to Kabat numbering system) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, V133T, S176V, T114A and S137K (according to Kabat numbering system); and / or (c) one or more of the following mutations in the VL: Q44R, Q44E, Q120C, Q44D and A49D (according to IMGT numbering system); and / or (d) one or more of the following mutations in the VH: Q44E, Q44R, G49C, Q44K and Q120K (according to IMGT numbering system). The above mutations are those of the “RUBY™ format”. In a further embodiment, the polypeptide may have a format as shown in Figure 23 with further optimised mutations, which is referred to as the “optimised RUBY™ format”. Although bispecific polypeptides in the “RUBY™ format” can be reproducibly produced with an excellent level of purity, bispecific polypeptides in the “optimised RUBY™ format” can be reproducibly produced at an even higher level of purity. Further, bispecific polypeptides in the “optimised RUBY™ format” have been engineered to carry a reduced risk of provoking immunogenic responses directed against the bispecific polypeptide itself. The optimised mutations are described below as “optimised mutation set 1” and “optimised mutation set 2” – including “set 2a” and / or “set 2b”. It will be appreciated by the skilled person various combinations of these optimised mutations could be used in a bispecific polypeptide, as well as in combination with any of the “RUBY™ format” mutations described above. The combinations of the “RUBY™ format” mutations and “optimised RUBY™ format” mutations, used in the same bispecific antibody, are described below. It will also be appreciated that the variations of those mutations as described herein would also work. All mutations in variable domains (VH or VL) are numbered according to the IMGT numbering system, and all mutations in the constant domains are numbered according to the EU numbering system. Mutation set 1 - Mutations in the variable domain heavy (VH): T65E, T65A, T65I. Mutation set 2 - any individual and / or any combination of the mutations listed in set 2a and set 2b. Set 2a - mutations in the CH1: Y180A, Y180G, Y180I, Y180N, Y180S, Y180T, Y180V, or Y180W, and / or S183N or S183T, and / or V188G; preferably, Y180T. Set 2b - mutations in the CKappa domain: A111R, A111T, A111W or A111V, and / or T109P; preferably: T109P and / or A111V; and / or mutations in the variable domain light (VL): I126A, I126G, I126H, I126N, I126P, I126Q, I126S, or I126T. In one embodiment, the mutations are at positions selected from the group consisting of: (a) the T65 position in the VH (according to the IMGT numbering system); and / or (b) one or more of the following positions in the CH1: Y180; S183; and V188, preferably Y180 (according to the EU numbering system); and / or (c) one or more of the following positions in the CKappa domain: A111 and T109 (according to the EU or Kabat numbering systems); and / or (d) the I126 position in the VL (according to the IMGT numbering system). In a particular embodiment, the mutation is at the T65 position in the variable domain heavy (VH)(according to the IMGT numbering system). In a particular embodiment, the mutations are one or more of the following positions in the CH1: Y180; S183; and V188, preferably Y180 (according to the EU numbering system). In a particular embodiment, the mutations are one or more of the following positions in the CKappa domain: A111 and T109 (according to the EU numbering system); and / or the I126 position in the VL (according to the IMGT numbering system). In one embodiment the mutations are selected from the group consisting of: (a) X65E / A / I in the VH (according to the IMGT numbering system); and / or (b) one or more of the following mutations in the CH1: X180A / G / I / N / S / T / V / W; X183N / T; and X188G; preferably, X180T (according to the EU numbering system); and / or (c) one or more of the following mutations in the CKappa domain: X111R / T / W / V; and X109P, preferably X111V and X109P (according to the EU or Kabat numbering systems); and / or (d) X126A / G / H / N / P / Q / S / T in the VL (according to the IMGT numbering system). *X refers to any amino acid In a particular embodiment, the mutation is X65E / A / I in the VH (according to the IMGT numbering system). *X refers to any amino acid In a particular embodiment, the mutation is one or more of the following mutations in the CH1: X180A / G / I / N / S / T / V / W; X183N / T; and X188G; preferably, X180T (according to the EU numbering system). *X refers to any amino acid In a particular embodiment, the mutation is one or more of the following mutations in the CKappa domain: X111R / T / W / V; and X109P, preferably X111V and X109P (according to the EU or Kabat numbering systems); and / or the mutation is X126A / G / H / N / P / Q / S / T in the VL (according to the IMGT numbering system). *X refers to any amino acid For example, the mutations may be selected from the group consisting of: (a) one or more of the following mutations in the VH: T65E; T65A; and T65I (according to the IMGT numbering system); and / or (b) one or more of the following mutations in the CH1: Y180A; Y180G; Y180I; Y180N; Y180S; Y180T; Y180V; Y180W; S183N; S183T; V188G, preferably Y180T (according to the EU numbering system); and / or (c) one or more of the following mutations in the CKappa domain: A111R; A111T; A111W; A111V; and T109P, preferably T109P and A111V (according to the EU or Kabat numbering systems); and / or (d) one or more of the following mutations in the VL: I126A; I126G; I126H; I126N; I126P; I126Q; I126S; and I126T (according to the IMGT numbering system). In a particular example, the mutations are one or more of the following mutations in the VH: T65E; T65A; and T65I (according to the IMGT numbering system). In a particular example, the mutations are one or more of the following mutations in the CH1: Y180A; Y180G; Y180I; Y180N; Y180S; Y180T; Y180V; Y180W; S183N; S183T; V188G, preferably Y180T (according to the EU numbering system). In a particular example, the mutations are one or more of the following mutations in the CKappa domain: A111R; A111T; A111W; A111V; and T109P, preferably T109P and A111V (according to the EU or Kabat numbering systems); and / or one or more of the following mutations in the VL: I126A; I126G; I126H; I126N; I126P; I126Q; I126S; and I126T (according to the IMGT numbering system). As discussed above, any combination of the “RUBY™ format” mutations and “optimised RUBY™ format” mutations can be used in the same bispecific polypeptide, such as any one or more of the following “RUBY™ format” mutations in (a) to (d), or variations described herein, being combined with any one or more of the following “optimised RUBY™ format” mutations in (e) to (g), or variations described herein: (a) one or more of the following mutations in the CH1 domain: H168A, F170G and / or T187E (according to EU numbering system); (b) one or more of the following mutations in the CKappa domain: L135Y, S176W, S114A and / or N137K (according to EU or Kabat numbering systems) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, T114A and / or S137K (according to Kabat numbering system); (c) mutations in the VL: Q44R or Q44E (according to IMGT numbering system); and (d) mutations in the VH: Q44E or Q44R (according to IMGT numbering system); (e) mutations in the VH: T65E, T65A or T65I (according to IMGT numbering system); (f) mutation in the CH1: Y180T (according to EU numbering system); and / or (g) mutations in the CKappa: T109P and / or A111V (according to EU or Kabat numbering systems). Accordingly, in a particular embodiment, a bispecific antibody with combined “RUBY™ format” mutations and “optimised RUBY™ format” mutations could include the following mutations: x one or more of the following mutations in the CH1 domain: H168A, F170G, Y180T and / or T187E (according to EU numbering system); x one or more of the following mutations in the CKappa domain: T109P, A111V, L135Y, S176W, S114A and / or N137K (according to EU or Kabat numbering systems) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, T114A and / or S137K (according to Kabat numbering system); x mutations in the VL: Q44R or Q44E (according to IMGT numbering system); and / or x one or more of the following mutations in the VH: Q44E or Q44R, and / or T65E, T65A or T65I (according to IMGT numbering system). In one embodiment, the one or more Fab fragment(s) is linked to the C-terminal end of the immunoglobulin via a linker. In one embodiment, the bispecific polypeptide is tetravalent, capable of binding bivalently to each of the two antigens. In one embodiment, the bispecific polypeptide comprises an immunoglobulin arranged as an antibody with two arms and therefore two binding sites for the first antigen, and two of the Fab fragments, each providing a binding site for the second antigen. Thus, there are two binding sites for the first antigen and two binding sites for the second antigen. The bispecific polypeptide of this embodiment may comprise three polypeptide chains: (1) chain H1 which comprises the heavy chain of the IgG a linker and the light chain of a Fab; (2) chain L1 is the light chain for the IgG; and (3) chain H2 is the heavy chain for the appended (attached) Fab. In a preferred embodiment, the bispecific polypeptide may comprise six polypeptide chains: (a) two chain H1, which comprise the heavy chain of the IgG a linker and the light chain of a Fab; (b) two chain L1, which are the light chain for the IgG; and (c) two chain H2, which are the heavy chain for the appended (attached) Fab. This structure can be used for both the “RUBY™ format” and “optimised RUBY™ format” antibodies. In one embodiment, binding domain B1 is an immunoglobulin and binding domain B2 is a Fab. In an alternative embodiment, binding domain B1 is a Fab and binding domain B2 is an immunoglobulin. In one embodiment, the bispecific polypeptide may modulate the activity of and / or activate a target immune system cell, wherein said modulation is an increase or decrease in the activity of said cell. Such cells include T cells, dendritic cells and natural killer cells. In another embodiment, the bispecific polypeptide may modulate the activity of and / or activate myeloid cells, such as macrophages, monocytes and myeloid-derived suppressor cells. Monocytes and macrophages also express CD40 and may promote immune responses against tumors. Indeed, the murine anti-CD40 surrogate antibody FGK45 was shown to be capable of mediating anti-tumor activity involving macrophages, independent of T cell and NK cell function (Lum HD, Buhtoiarov IN, Schmidt BE, et al. In vivo CD40 ligation can induce T-cell-independent antitumor effects that involve macrophages. J Leukoc Biol. 2006 Jun;79(6):1181-92). However, the effects of CD40 agonists on macrophages and other myeloid cell populations also result in increased production of IFN-DŽ and CCL5, which promote improved influx of T cells to the tumor (Huffman AP, Lin JH, Kim SI, et al. CCL5 mediates CD40-driven CD4+ T cell tumor infiltration and immunity. JCI Insight. 2020 May 21;5(10)). Several studies have indicated that CD40 agonist antibodies can convert TAM into activated macrophages with an anti-tumor phenotype. FGK45 interacts with TAM following treatment in vivo, and results in their increased expression of MHCII and CD86 (Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011 Mar 25;331(6024):1612-6). Similar effects have been observed on CD11b+F4 / 80+macrophages in the spleen (Luheshi NM, Coates-Ulrichsen J, Harper J, et al. Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model. Oncotarget. 2016 Apr 5;7(14):18508-20), and the liver, where the treatment may result in hepatotoxicity due to the strong effect on macrophages (Byrne KT, Vonderheide RH. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer. Cell Rep. 2016 Jun 21;15(12):2719-32; Medina-Echeverz J, Ma C, Duffy AG, et al. Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage. Cancer Immunol Res.2015 May;3(5):557-66). Interestingly, aged and obese mice were shown to be more susceptible to systemic toxicity after immunotherapy such as anti-CD40, and it was further demonstrated that macrophages were the cells primarily responsible for these effects (Bouchlaka MN, Sckisel GD, Chen M, et al. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy. J Exp Med. 2013 Oct 21;210(11):2223-37; Mirsoian A, Bouchlaka MN, Sckisel GD, et al. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. J Exp Med. 2014 Nov 17;211(12):2373-83). Macrophage-mediated hepatotoxicity following anti-CD40 treatment was later shown to be alleviated by combination treatment with anti-CSF-1R antibody, which blocked CSF-1R signalling supporting differentiation, proliferation and function of monocytes and macrophages (Byrne KT, Vonderheide RH. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer. Cell Rep. 2016 Jun 21;15(12):2719- 32). Combination therapy with anti-CD40 and anti-CSF-1R is currently being explored in clinical studies (Machiels JP, Gomez-Roca C, Michot JM, et al. Phase Ib study of anti- CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients. J Immunother Cancer. 2020 Oct;8(2)). The immune system cell (for example, the target immune cell) is typically a dendritic cell. For example, the bispecific polypeptide may be capable of inducing activation of dendritic cells, which are then capable of internalising tumour associated debris or extracellular vesicles containing CEA and tumour neoantigens. For example, the polypeptide may be capable of inducing: (a) tumour-specific immune activation; and / or (b) activation of dendritic cells; and / or (c) internalisation of associated tumour debris and / or extracellular vesicles containing CEA as well as tumour neoantigens; and / or (d) cross-presentation of peptides derived from internalised tumour antigens on MHC; and / or (e) priming and activation of effector T cells; and / or (f) direct tumoricidal effects, selected from the list consisting of: apoptosis, necroptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement- dependent cytotoxicity (CDC). It will be appreciated by persons skilled in the art, that said activation of dendritic cells may be an increase in the expression of the co-stimulatory molecules CD40, CD80 or CD86, or increased IL-12 production. Alternatively, activation of dendritic cells can be determined by the increased ability to cross-present antigens, e.g. tumour neoantigens, on MHC class I or II to T cells, generating an enhanced activation of T cells recognizing said antigen, by the antigen-presenting cell. In one embodiment, the bispecific antibody induces an increase in the uptake of tumour debris or tumour extracellular vesicles by an antigen-presenting cell, such as a dendritic cell. It will be appreciated by persons skilled in the art, that said increase in uptake may be measured by the co-localization or internalization of the tumour debris or tumour extracellular vesicles by the antigen-presenting cell. The increased uptake of tumour debris or tumour extracellular vesicles by the antigen- presenting cells would subsequently result in an effective presentation of neoantigens contained within the tumour debris or tumour extracellular vesicles in the context of MHC molecules, which in turn results in a broader tumor specific T cell repertoire and, thus, more effective T cell-mediated tumour eradication. Methods for determining the expansion of tumour-antigen specific T cells are well known and include, for example, the use of MHC-peptide multimers, e.g. tetramers or pentamers. Such expansion may be measured by inoculating mice with tumours expressing a specific tumour antigen or tumours transfected with a tumour model antigen (e.g., ovalbumin), alternatively by inoculating mice with the same cells that have been heat shocked to induce necrosis, followed by measuring the expansion of tumour antigen-specific T cells by use of various MHC-tumour (model) antigen peptide tetramers or pentamers by flow cytometry-based methods. Alternatively, such expansion may be measured by culturing dendritic cells with antigen-specific TCR transgenic T cells labelled with a proliferative dye and tumour debris or tumour-derived extracellular vesicles derived from tumours transfected with a model antigen (e.g., ovalbumin). Expansion of the antigen-specific T cells can be assessed by analysing dilution of the proliferative dye using flow cytometry. The bispecific polypeptide or binding domains can also be characterised and defined by their binding abilities. Standard assays to evaluate the binding ability of ligands towards targets are well known in the art, including for example, ELISA, Western blot, RIA, and flow cytometry analysis. The binding kinetics (e.g., binding affinity) of the polypeptide can also be assessed by standard assays known in the art, such as by surface plasmon resonance analysis or bio-layer interferometry. The terms "binding activity" and "binding affinity" are intended to refer to the tendency of a polypeptide molecule to bind or not to bind to a target. Binding affinity may be quantified by determining the dissociation constant (KD) for a polypeptide and its target. A lower KD is indicative of a higher affinity for a target. Similarly, the specificity of binding of a polypeptide to its target may be defined in terms of the comparative dissociation constants (KD) of the polypeptide for its target as compared to the dissociation constant with respect to the polypeptide and another, non-target molecule. The value of this dissociation constant can be determined directly by well-known methods, and can be computed even for complex mixtures by methods such as those, for example, set forth in Caceci et al., 1984 (the disclosures of which are incorporated herein by reference). For example, the KDmay be established using a double-filter nitrocellulose filter binding assay such as that disclosed by Wong & Lohman, 1993. Other standard assays to evaluate the binding ability of ligands such as antibodies towards targets are known in the art, including for example, ELISA, Western blot, RIA, and flow cytometry analysis. The binding kinetics (e.g., binding affinity) of the polypeptide also can be assessed by standard assays known in the art, such as by surface plasmon resonance (by use of e.g., Biacore™ system analysis) or by bio-layer interferometry (by use of e.g. Octet®system analysis). A competitive binding assay can be conducted in which the binding of the polypeptide to the target is compared to the binding of the target by another, known ligand of that target, such as another polypeptide. The concentration at which 50% inhibition occurs is known as the Ki. Under ideal conditions, the Ki is equivalent to KD. The Ki value will never be less than the KD, so measurement of Ki can conveniently be substituted to provide an upper limit for KD. Alternative measures of binding affinity include EC50 or IC50. In this context EC50 indicates the concentration at which a polypeptide achieves 50% of its maximum binding to a fixed quantity of target. IC50 indicates the concentration at which a polypeptide inhibits 50% of the maximum binding of a fixed quantity of competitor to a fixed quantity of target. In both cases, a lower level of EC50 or IC50 indicates a higher affinity for a target. The EC50 and IC50 values of a ligand for its target can both be determined by well-known methods, for example ELISA. Suitable assays to assess the EC50 and IC50 of polypeptides are set out in the Examples. In one embodiment, the bispecific polypeptide is preferably capable of binding to its target with an affinity that is at least two-fold, 10-fold, 50-fold, 100-fold or greater than its affinity for binding to another non-target molecule. In one embodiment, the bispecific polypeptide is capable of: (a) activation of a B-cell, in the presence of a CEA (preferably CEACAM5); and / or (b) activation of dendritic cells in the presence of CEA (preferably CEACAM5); and / or (c) capable of increased dendritic cell cross-presentation of neoantigens; and / or (d) inducing proliferation of neoantigen specific T cells. In one embodiment, the bispecific polypeptide promotes uptake of tumor derived material, derived from tumor cells overexpressing CEA (preferably CEACAM5). In a particular embodiment, the uptake of tumor derived material is by antigen presenting cells. It will be appreciated by persons skilled in the art, that said activation of B-cell activation can be characterised by CD86 upregulation, as well as, optionally, other markers of B-cell activation. CD40 binding domains The bispecific polypeptide comprises a binding domain (B1) which is capable of specifically binding to CD40. Preferably, B1 is an agonistic CD40 binding domain. Binding domain B1 specifically binds to CD40, i.e. it binds to CD40 but does not bind, or binds at a lower affinity, to other molecules. The term CD40, as used herein, typically refers to human CD40. The sequence of human CD40 is set out in GenBank: X60592.1. Binding domain B1 may have some binding affinity for CD40 from other mammals, such as CD40 from a non-human primate (for example Macaca fascicularis (cynomolgus monkey), Macaca mulatta). Binding domain B1 preferably does not bind to murine CD40 and / or does not bind to other human TNFR superfamily members, for example human CD137 or OX40. Advantageously, binding domain B1 binds to human CD40 with a KD of less than 2x10-7M or less than 1.5x10-7M or less than 8.5x10-8M or less than 8x10-8M or less than 7.5x10-8M or less than 7x10-8M or less than 9x10-8M or less than 9x10-9M or less than 5x10-10M or less than 3x10-10M, preferably less than 8.5x10-8M, more preferably less than 5x10-10M or less than 3x10-10M. Preferably, the KDis measured in Octet; for example, as explained in the Examples. For example, binding domain B1 preferably does not bind to murine CD40 or any other TNFR superfamily member, such as CD137 or OX40. Therefore, typically, the KD for the binding domain with respect to human CD40 will be 2-fold, preferably 5-fold, more preferably 10-fold less than KDwith respect to the other, non-target molecules, such as murine CD40, other TNFR superfamily members, or any other unrelated material or accompanying material in the environment. More preferably, the KD will be 50-fold less, even more preferably 100-fold less, and yet more preferably 200-fold less. Binding domain B1 is preferably capable of binding to its target with an affinity that is at least two-fold, 10-fold, 50-fold, 100-fold or greater than its affinity for binding to another non-target molecule. In summary therefore, binding domain B1 preferably exhibits at least one of the following functional characteristics: a) binding to human CD40 with a KDvalue which is less than 2x10-7M, more preferably less than 5x10-10M; b) does not bind to murine CD40; c) does not bind to other human TNFR superfamily members, for example human CD137 or OX40. In one embodiment, binding domain B1 comprises one or more light chain CDR sequences selected from those in Table C(2), and / or one or more heavy chain CDR sequences selected from Table C(1). Thus binding domain B1 may comprise one or more CDR sequences selected from the groups consisting of: (a) CD40 heavy chain CDRs, SEQ ID NOs: 73 to 89; and / or (b) CD40 light chain CDRs, SEQ ID NOs: 90 to 104. In one embodiment binding domain B1 comprises one, two or three light chain CDR sequences from a particular row for an individual antibody reference in Table C(2), and / or one, two or three heavy chain CDR sequences from the corresponding row for the antibody with the same reference in Table C(1). For example, binding domain B1 might comprise one or more of the light chain CDR sequences for 1132 (SEQ ID NOs: 90, 91 and 92) and one or more of the heavy chain CDR sequences for 1132 (SEQ ID NOs: 73, 74 and 75), or binding domain B1 might comprise one or more of the light chain CDR sequences for 1132 (SEQ ID NOs: 96, 97 and 98) and one or more of the heavy chain CDR sequences for 1132 (SEQ ID NOs: 81, 82 and 83). Most preferably, B1 comprises the CDRs and / or the VL and VH of 1132. Also most preferably, B1 comprises the CDRs and / or the VL and VH of G12 or G12-mut. The CDRs of G12-mut are shared by ffAC_05337. Accordingly, in a preferred embodiment B1 comprises the CDRs of ffAC_05337, which are SEQ ID NOs: 81-83 and 96-98. Preferred CD40 binding domains may comprise at least a heavy chain CDR3 as defined in any individual row of Table C(1) and / or a light chain CDR3 as defined in in any individual row of Table C(2). Accordingly, in one embodiment binding domain B1 comprises all six CDR sequences for a given antibody (VH / VL) reference, for example binding domain B1 might comprise all six CDR sequences of antibody 1132 or all six CDR sequences of antibody G12 (as also present in G12_mut and ffAC_05337). In one embodiment, binding domain B1 comprises a VH and / or a VL amino acid sequence as given in Table A. In one embodiment, binding domain B1 comprises a VH and VL amino acid sequence as given in Table A for a particular antibody reference. For example, binding domain B1 may comprise the VH sequence of 1132 (SEQ ID NO: 3) and / or the VL sequence of 1132 (SEQ ID NO: 1), or the VH sequence of G12 (SEQ ID NO: 19) and / or the VL sequence of G12 (SEQ ID NO: 17), the VH sequence of G12- mut (SEQ ID NO: 29) and / or the VL sequence of G12_mut (SEQ ID NO: 17), the VH sequence of ffAC_05337 (SEQ ID NO: 431) and / or the VL sequence of ffAC_05337 (SEQ ID NO: 430). In a preferred embodiment B1 comprises the VL and VH of ffAC_05337, which are SEQ ID NO: 430 and 431. In one embodiment the CD40 binding domain of B1 is selected from: 1132; 1150, 1140, 1107, G12, APX005 and 21.4.1. Preferably, the CD40 binding domain of B1 is G12 and / or 1132. Most preferably, the CD40 binding domain of B1 is G12. In an alternative most preferred embodiment, the CD40 binding domain of B1 is G12_mut. Thus, the CDR or VH and VL sequences of binding domain B1 might be selected from antibodies from the group consisting of: (a) 1132 (heavy chain CDRs: SEQ ID NOs: 73, 74 and 75; light chain CDRs: SEQ ID NOs: 90, 91, and 92; VL: SEQ ID NO: 1; VH: SEQ ID NO: 3) (b) 1150 (heavy chain CDRs: SEQ ID NOs: 73, 76 and 77; light chain CDRs: SEQ ID NOs: 90, 91, and 93; VL: SEQ ID NO: 5; VH: SEQ ID NO: 7) (c) 1140 (heavy chain CDRs: SEQ ID NOs: 73, 78 and 79; light chain CDRs: SEQ ID NOs: 90, 91, and 94; VL: SEQ ID NO: 9; VH: SEQ ID NO: 11) (d) 1107 (heavy chain CDRs: SEQ ID NOs: 73, 78 and 80; light chain CDRs: SEQ ID NOs: 90, 91, and 95; VL: SEQ ID NO: 13; VH: SEQ ID NO: 15) (e) G12 (heavy chain CDRs: SEQ ID NOs: 81, 82 and 83; light chain CDRs: SEQ ID NOs: 96, 97, and 98; VL: SEQ ID NO: 17; VH: SEQ ID NO: 19) (f) APX005 (heavy chain CDRs: SEQ ID NOs: 84, 85 and 86; light chain CDRs: SEQ ID NOs: 99, 100, and 101; VL: SEQ ID NO: 21; VH: SEQ ID NO: 23) (g) 21.4.1 (heavy chain CDRs: SEQ ID NOs: 87, 88 and 89; light chain CDRs: SEQ ID NOs: 102, 103, and 104; VL: SEQ ID NO: 25, VH: SEQ ID NO: 27) (h) G12_mut (heavy chain CDRs: SEQ ID NOs: 81, 82 and 83; light chain CDRs: SEQ ID NOs: 96, 97, and 98; VL: SEQ ID NO: 17; VH: SEQ ID NO: 29) (i) ffAC_05337 (heavy chain CDRs: SEQ ID NOs: 81, 82 and 83; light chain CDRs: SEQ ID NOs: 96, 97, and 98; VL: SEQ ID NO: 431; VH: SEQ ID NO: 430). The numbering of the antibody (e.g. Antibody X / Y) defines the heavy chain variable region (X) and the light chain variable region (Y), respectively (or, where a single number is indicated, the heavy chain variable region [X] only is defined). As described above, the sequences may be one or more CDR sequence, or the VH and / or VL sequence. As described above, the sequences of the bispecific polypeptide may comprise specified mutations. In one embodiment binding domain B1 is specific for CD40, typically human CD40 and may comprise any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which consists of the sequence “G, F, T, F, S, S, Y, A”; (b) a heavy chain CDR2 sequence which is 8 amino acids in length and comprises the consensus sequence: “I, G / S, S / G, Y / S, G / S, G / S, G / Y / S, T”; (c) a heavy chain CDR3 sequence which is 9 to 12 amino acids in length and which comprises the consensus sequence of : “A, R, Y / R / G, Y / P / V / -, N / S / V, F / Y / W, G / H / S, - / S, - / V, M / F, D, Y” (d) a light chain CDR1 sequence which consists of the sequence: “Q, S, I, S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which is 9 amino acids in length and comprises the consensus sequence: “Q,Q, Y / S, G / Y, R / S / V, N / A / Y / T, P, P / F / Y, T”. The use of “,” in the context of discussing amino acid sequences is to illustrate a list of amino acids when further nomenclature, such as “ / ”, is included; for example, “G, F, T, F, S, S, Y, A” indicates that the sequence of amino acids is GFTFSSYA and “A, R, Y / R / G” indicates that the sequence of amino acids could be ARY or ARR or ARG. The use of “-” in the context of discussing amino acid sequences is to illustrate that there might not be an amino acid present at that respective position; for example, “- / V, M / F, D” indicates that the sequence of amino acids could be VMD or VFD or MD or FD. Binding domain B1 may comprise at least a heavy chain CDR3 as defined in (c) and / or a light chain CDR3 as defined in (f). Binding domain B1 may comprise all three heavy chain CDR sequences of (a), (b) and (c) and / or all three light chain CDR sequences of (d), (e) and (f). Examples of complete heavy and light chain variable region amino acid sequences for binding domain B1 are shown in Table A. Exemplary nucleic acid sequences encoding each amino acid sequence are also shown. The numbering of said VH and VL regions in Table A corresponds to the numbering system used as in Table C(1) and C(2). Thus, for example, the amino acid sequence for “1132, light chain VL (also known as 1133)” is an example of a complete VL region sequence comprising all three CDRs of VL number 1132 (1133) shown in Table C(2) and the amino acid sequence for “1132, heavy chain VH” is an example of a complete VH region sequence comprising all three CDRs of VH number 1132 shown in Table C(1). In exemplary embodiments, binding domain B1 comprises: (a) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1132 / 1133 (SEQ ID NOs: 73, 74 and 75; and / or SEQ ID NOs: 90, 91, and 92); (b) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1150 / 1151 (SEQ ID NOs: 73, 76 and 77; and / or SEQ ID NOs:90, 91, and 93); (c) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1140 / 1135 (SEQ ID NOs: 73, 78 and 79; and / or SEQ ID NOs: 90, 91, and 94); (d) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1107 / 1108 (SEQ ID NOs: 73, 78 and 80; and / or SEQ ID NOs: 90, 91, and 95); (e) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody G12 or G12_mut or ffAC_05337 (SEQ ID NOs: 81, 82 and 83; and / or SEQ ID NOs: 96, 97, and 98); (f) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody APX005 (SEQ ID NOs: 84, 85 and 86; and / or SEQ ID NOs: 99, 100, and 101); or (g) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 21.4.1 (SEQ ID NOs: 87, 88 and 89; and / or SEQ ID NOs: 102, 103, and 104). Thus, binding domain B1 may comprise: (a) the heavy chain variable region and / or the light chain variable region of antibody 1132 / 1133 (SEQ ID NO: 3 and / or SEQ ID NO: 1); (b) the heavy chain variable region and / or the light chain variable region of antibody 1150 / 1151 (SEQ ID NO: 7 and / or SEQ ID NO: 5); (c) the heavy chain variable region and / or the light chain variable region of antibody 1140 / 1135 (SEQ ID NO: 11 and / or SEQ ID NO: 9); (d) the heavy chain variable region and / or the light chain variable region of antibody 1107 / 1108 (SEQ ID NO:15 and / or SEQ ID NO: 13); (e) the heavy chain variable region and / or the light chain variable region of antibody G12 (SEQ ID NO: 19 and / or SEQ ID NO: 17); (f) the heavy chain variable region and / or the light chain variable region of antibody APX005 (SEQ ID NO: 23 and / or SEQ ID NO: 21); (g) the heavy chain variable region and / or the light chain variable region of antibody 21.4.1 (SEQ ID NO: 27 and / or SEQ ID NO: 25); (h) the heavy chain variable region and / or the light chain variable region of antibody G12_mut (SEQ ID NO: 29 and / or SEQ ID NO: 17); or (h) the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NO: 431 and / or SEQ ID NO: 430). In an exemplary embodiment, binding domain B1 comprises: the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1132 / 1133 (SEQ ID NOs: 73, 74 and 75 and / or SEQ ID NOs: 90, 91, and 92), or the exemplary heavy and light chain variable regions (SEQ ID NO: 3 and SEQ ID NO: 1), or heavy and light antibody chains, which comprise said CDRs, as detailed above. In a further exemplary embodiment, binding domain B1 comprises: the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody G12 (SEQ ID NOs: 81, 82 and 83 and / or SEQ ID NOs: 96, 97 and 98), or the exemplary heavy and light chain variable regions (SEQ ID NO: 19 and SEQ ID NO: 17), or heavy and light antibody chains, which comprise said CDRs, as detailed above. In a further exemplary embodiment, binding domain B1 comprises: the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody G12_mut (SEQ ID NOs: 81, 82 and 83 and / or SEQ ID NOs: 96, 97 and 98), or the exemplary heavy and light chain variable regions (SEQ ID NO: 29 and SEQ ID NO: 17), or heavy and light antibody chains, which comprise said CDRs, as detailed above. In a further, and preferred, exemplary embodiment, binding domain B1 comprises: the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody ffAC_05337 (SEQ ID NOs: 81, 82 and 83 and / or SEQ ID NOs: 96, 97 and 98), or the exemplary heavy and light chain variable regions (SEQ ID NO: 431 and SEQ ID NO: 430), or heavy and light antibody chains, which comprise said CDRs, as detailed above. The numbering of the antibody (e.g. Antibody X / Y) defines the heavy chain variable region (X) and the light chain variable region (Y), respectively (or, where a single number is indicated, the heavy chain variable region [X] only is defined). It will be appreciated by persons skilled in the art that the bispecific polypeptides may alternatively comprise variants of the above-defined variable regions (or variants of the CDR sequences of the B1 and / or B2 binding domains). A variant of any one of the heavy or light chain amino acid sequences or CDR sequences recited herein may be a substitution, deletion or addition variant of said sequence. A variant may comprise 1, 2, 3, 4, 5, up to 10, up to 20, up to 30 or more amino acid substitutions and / or deletions from the said sequence. “Deletion” variants may comprise the deletion of individual amino acids, deletion of small groups of amino acids such as 2, 3, 4 or 5 amino acids, or deletion of larger amino acid regions, such as the deletion of specific amino acid domains or other features. "Substitution" variants preferably involve the replacement of one or more amino acids with the same number of amino acids and making conservative amino acid substitutions. For example, an amino acid may be substituted with an alternative amino acid having similar properties, for example, another basic amino acid, another acidic amino acid, another neutral amino acid, another charged amino acid, another hydrophilic amino acid, another hydrophobic amino acid, another polar amino acid, another aromatic amino acid or another aliphatic amino acid. Some properties of the 20 main amino acids which can be used to select suitable substituents are as follows: Ala, A aliphatic, hydrophobic, neutral Met, M hydrophobic, neutral Cys, C polar, hydrophobic, neutral Asn, N polar, hydrophilic, neutral Asp, D polar, hydrophilic, charged (-) Pro, P hydrophobic, neutral Glu, E polar, hydrophilic, charged (-) Gln, Q polar, hydrophilic, neutral Phe, F aromatic, hydrophobic, neutral Arg, R polar, hydrophilic, charged (+) Gly, G aliphatic, neutral Ser, S polar, hydrophilic, neutral His, H aromatic, polar, hydrophilic, charged (+) Thr, T polar, hydrophilic, neutral Ile, I aliphatic, hydrophobic, neutral Val, V aliphatic, hydrophobic, neutral Lys, K polar, hydrophilic, charged (+) Trp, W aromatic, hydrophobic, neutral Leu, L aliphatic, hydrophobic, neutral Tyr, Y aromatic, polar, hydrophobic Amino acids herein may be referred to by full name, three letter code or single letter code. Preferred "derivatives" or "variants" include those in which instead of the naturally occurring amino acid the amino acid which appears in the sequence is a structural analog thereof. Amino acids used in the sequences may also be derivatised or modified, e.g. labelled, providing the function of the polypeptide is not significantly adversely affected. Derivatives and variants as described above may be prepared during synthesis of the polypeptide or by post-production modification, or when the polypeptide is in recombinant form using the known techniques of site-directed mutagenesis, random mutagenesis, or enzymatic cleavage and / or ligation of nucleic acids. Preferably variants have an amino acid sequence which has more than 60%, or more than 70%, e.g. 75 or 80%, preferably more than 85%, e.g. more than 90 or 95% amino acid identity to a sequence as shown in the sequences disclosed herein. This level of amino acid identity may be seen across the full length of the relevant SEQ ID NO sequence or over a part of the sequence, such as across 20, 30, 50, 75, 100, 150, 200 or more amino acids, depending on the size of the full-length polypeptide. In connection with amino acid sequences, "sequence identity" refers to sequences which have the stated value when assessed using ClustalW (Thompson et al., 1994; the disclosures of which are incorporated herein by reference) with the following parameters: Pairwise alignment parameters - Method: accurate, Matrix: PAM, Gap open penalty: 10.00, Gap extension penalty: 0.10. Multiple alignment parameters - Matrix: PAM, Gap open penalty: 10.00, % identity for delay: 30, Penalize end gaps: on, Gap separation distance: 0, Negative matrix: no, Gap extension penalty: 0.20, Residue-specific gap penalties: on, Hydrophilic gap penalties: on, Hydrophilic residues: GPSNDQEKR. Sequence identity at a particular residue is intended to include identical residues which have simply been derivatised. In one embodiment, binding domain B1 comprises the light chain of antibody 1132 / 1133 (SEQ ID NO: 372 or 379) and / or the heavy chain of antibody 1132 / 1133 (SEQ ID NO: 371 or 378). In one embodiment, binding domain B1 comprises the light chain of antibody G12 (SEQ ID NO: 381) and / or the heavy chain of antibody G12 (SEQ ID NO: 380). In one embodiment, binding domain B1 comprises the light chain of antibody G12_mut (SEQ ID NO: 383) and / or the heavy chain of antibody G12_mut (SEQ ID NO: 382). It will be appreciated by the skilled person, and it is included herein, that mutations described herein for the RUBYTMformat and / or the optimised RUBYTMformat can be applied to the above light chain and / or the heavy chain sequences of G12 and / or G12_mut. Thus, in one embodiment binding domain B1 may comprise one or more variants of the above-defined light chain variable regions and / or said heavy chain variable regions (and / or light chain and / or said heavy chain) having at least 90% sequence identity thereto or 95% sequence identity thereto or 99% sequence identity thereto. Binding domain B1 may also comprise variants of the CDR sequences specified herein, for example variants where up one, two, three, four or five amino acid residues are substituted, deleted to added compared to the specified reference sequences. For reference, the antibody reference used in this application, possible alternative names for the same antibody / binding domain, and the target of the antibody / binding domain, is laid out in Table i below. Table i: Alternative names for particular CD40 antibodies / binding domains Antibody Alternative names reference 1132 1132 / 1133 1150 1150 / 1151 1140 1140 / 1135 1107 1107 / 1108 G12 ADC-1013 APX005 21.4.1 G12_mut The “G12_mut” antibody largely corresponds to the sequence of “G12”; however, G12_mut includes three mutations in the VH framework . The CDRs and the VL sequences of G12_mut are the same as the G12. Carcinoembryonic antigen (CEA) binders The bispecific polypeptides further comprise a binding domain (B2) which is capable of specifically binding a carcinoembryonic antigen (CEA). Binding domain B2 specifically binds to CEA, i.e. it binds to CEA but does not bind, or binds at a lower affinity, to other molecules. The term CEA, as used herein, typically refers to human CEA. Binding domain B2 may have some binding affinity for CEA from other mammals, such as CEA from a non-human primate (for example Macaca fascicularis (cynomolgus monkey), Macaca mulatta). Binding domain B2 preferably does not bind to non-target molecules, such as CTLA-4-Fc and / or human ubiquitin. In one embodiment, the CEA is a tumor-associated CEA. By “tumor-associated CEA” we include a member of the CEA family whose presence and / or overexpression is correlated with the existence of cancer and / or tumours; for example, a CEA that is known or suspected to be overexpressed by cancer and / or tumour cells. Members of the CEA family that are associated with tumours and / or cancer would be known to the skilled person; for example, CEACAM1, CEACAM6, CEACAM7 and / or CEACAM5. In one embodiment, the CEA is a carcinoembryonic antigen-related cell adhesion molecule (CEACAM). In one embodiment, the CEACAM is one or more selected from the listing consisting of: CEACAM1 (such as, GenBank: NG_029051.2); CEACAM3 (such as, GenBank: D90278.1); CEACAM4 (such as, GenBank: D90276.1); CEACAM5 (such as, GenBank: M17303.1); CEACAM6 (such as, GenBank: M29541.1); CEACAM7 (such as, GenBank: L31792.1); CEACAM8 (such as, GenBank: X52378.1); CEACAM16 (such as, GenBank: EU021223.1); CEACAM18 (such as, GenBank: AC020914.9); CEACAM19 (such as, GenBank: BC083499.1); CEACAM20 (such as, GenBank: AY358129.1); and CEACAM21 (such as, GenBank: BC106727.1). It will be appreciated that the reference to the aforementioned CEACAM molecules includes splice variants. Preferably, the CEACAM is one or more selected from the listing consisting of: CEACAM1; CEACAM5; and CEACAM6. Preferably, the CEACAM is CEACAM1. Most preferably, the CEACAM is CEACAM5. In a preferred embodiment, B2 is capable of specifically binding to CEACAM5 but not other CEACAMs, particularly not CEACAM1. In one embodiment, B2 which is capable of specifically binding to CEA on a target cell. Preferably, the target cell is a cancer cell and / or a tumour cell. Preferably, the CEA on the target cell is an intermediate level of CEA or a high level of CEA. In one embodiment, the intermediate level of CEA expression is characterised by the target cell expressing about 10,000 or more CEA receptors per target cell; for example, about 11,000 or more; about 12,000 or more; about 13,000 or more; about 14,000 or more; about 15,000 or more; about 16,000 or more; about 17,000 or more; about 18,000 or more; about 19,000 or more; about 20,000 or more; about 25,000 or more; about 30,000 or more; about 35,000 or more; about 40,000 or more; about 50,000 or more; about 60,000 or more; about 70,000 or more; about 80,000 or more; about 90,000 or more; about 100,000 or more; about 125,000 or more; about 150,000 or more; or about 175,000 or more CEA receptors per target cell. In another embodiment, the intermediate level of CEA expression is characterised by the target cell expressing about 10,000 to about 200,000 CEA receptors per target cell; for example, about 20,000 to about 175,000 CEA receptors per target cell or 20,000 to about 200,000 CEA receptors per target cell or about 50,000 to about 175,000 CEA receptors per target cell or about 50,000 to about 200,000 CEA receptors per target cell. Preferably, the CEA receptors are CEACAM5 receptors. In one embodiment, the high level of CEA expression is characterised by the target cell expressing about 200,000 or more CEA receptors per target cell; for example, about 225,000 or more; about 250,000 or more; about 275,000 or more; about 300,000 or more; about 325,000 or more; about 350,000 or more; about 375,000 or more; about 400,000 or more; about 425,000 or more; about 450,000 or more; about 475,000 or more; about 500,000 or more; about 600,000 or more; about 700,000 or more; about 800,000 or more; about 900,000 or more; or about 1,000,000 CEA receptors per target cell, preferably about 300,000 of more CEA receptors per target cell. In another embodiment, the high level of CEA expression is characterised by the target cell expressing about 200,000 to about 1,000,000 CEA receptors per target cell; for example, about 200,000 to about 500,000 CEA receptors per target cell or about 300,000 to about 500,000 CEA receptors per target cell. Preferably, the CEA receptors are CEACAM5 receptors. In one embodiment, B2 is not capable of specifically binding to a cell with no CEA expression or a low level of CEA expression. In one embodiment, the low level of CEA expression is characterised by a cell expressing about 10,000 or fewer CEA receptors per cell; for example, about 9,000 or fewer; about 8,000 or fewer; about 7,000 or fewer; about 6,000 or fewer; about 5,000 or fewer; about 4,000 or fewer; about 3,000 or fewer; about 2,000 or fewer; or about 1,000 or fewer CEA receptors per cell. Advantageously, binding domain B2 binds to human CEA with a KDof less than 2x10-6M or less than 1.5x10-8M or less than 2.5x10-9M or less than 2x10-9M or less than 1.5x10-12M or less than 1x10-12M, preferably less than 1.5x10-8M or less than 2.5x10-9M or less than 1.5x10-12M. Preferably, the KDis measured in Octet; for example, as explained in the Examples. For example, binding domain B2 preferably does not bind to non-target molecules, such as CTLA-4-Fc and / or human ubiquitin. In a particular embodiment relating to a specific CEACAM, the non-target molecule may be a different CEACAM; for example, for CEACAM5 the non-target molecule may be CEACAM, and vice versa. Therefore, typically, the KDfor the binding domain with respect to human CEA will be 2-fold, preferably 5-fold, more preferably 10-fold less than KD with respect to the other, non- target molecules, such as CTLA-4-Fc and / or human ubiquitin or any other unrelated material or accompanying material in the environment. More preferably, the KDwill be 50-fold less, even more preferably 100-fold less, and yet more preferably 200-fold less. Binding domain B2 is preferably capable of binding to its target with an affinity that is at least two-fold, 10-fold, 50-fold, 100-fold or greater than its affinity for binding to another non-target molecule. In summary therefore, binding domain B2 preferably exhibits at least one of the following functional characteristics: a) binding to human CEA with a KD value which is less than 2x10-6M, more preferably less than 2.5x10-9M or less than 1.5x10-12M, more preferably less than 1.5x10-12M; b) does not bind to non-target molecules, such as CTLA-4-Fc and / or human ubiquitin. In one embodiment, binding domain B2 binds preferentially to CEA on a cell over soluble CEA. By “binds preferentially to CEA on a cell over soluble CEA”, we include that when in the presence of CEA on a cell (such as, on the surface of a cell) and soluble CEA, B2 will be more likely to bind to CEA on the cell than the soluble CEA. In one embodiment, binding domain B2 comprises one or more light chain CDR sequences selected from those in Table D(2) and / or one or more heavy chain CDR sequences selected from Table D(1a) and / or Table D(1b). Thus binding domain B2 may comprise one or more CDR sequences selected from the groups consisting of: (a) CEA heavy chain CDRs, SEQ ID NOs: 216 to 310, 335; and / or (b) CEA light chain CDRs, SEQ ID NOs: 90, 91, 94, 311 to 334. In one embodiment binding domain B2 comprises one, two or three light chain CDR sequences from a particular row for an individual antibody reference in Table D(2), and / or one, two or three heavy chain CDR sequences from the corresponding row for the antibody with the same reference in Table D(1a) and / or Table D(1b). For example, binding domain B2 might comprise one or more of the light chain CDR sequences for AC_05059 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05059 (SEQ ID NOs: 216, 217, and 218 or 280, 281 and 218) or one or more of the light chain CDR sequences for AC_05060 (SEQ ID NOs: 312, 91, and 313) and one or more of the heavy chain CDR sequences for AC_05060 (SEQ ID NOs: 219, 220, and 221 or 282, 283 and 221) or one or more of the light chain CDR sequences for AC_05061 (SEQ ID NOs: 90, 91 and 314) and one or more of the heavy chain CDR sequences for AC_05061 (SEQ ID NOs: 222, 223 and 224 or 284, 285 and 224) or one or more of the light chain CDR sequences for AC_05062 (SEQ ID NOs: 315, 316 and 94) and one or more of the heavy chain CDR sequences for AC_05062 (SEQ ID NOs: 222, 223 and 225 or 284, 285 and 225) or one or more of the light chain CDR sequences for AC_05064 (SEQ ID NOs: 90, 91 and 317) and one or more of the heavy chain CDR sequences for AC_05064 (SEQ ID NOs: 222, 223 and 226 or 284, 285 and 226) or one or more of the light chain CDR sequences for AC_05079 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05079 (SEQ ID NOs: 216, 217 and 227 or 280, 281 and 227) or one or more of the light chain CDR sequences for AC_05081 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05081 (SEQ ID NOs: 216, 217 and 229 or 280, 281 and 229) or one or more of the light chain CDR sequences for AC_05088 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05088 (SEQ ID NOs: 216, 217 and 237 or 280, 281 and 237) or one or more of the light chain CDR sequences for AC_05089 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05089 (SEQ ID NOs: 216, 217, and 238 or 280, 281 and 238) or one or more of the light chain CDR sequences for AC_05090 (SEQ ID NOs: 90, 91, and 311) and one or more of the heavy chain CDR sequences for AC_05090 or ffAC_05337 (SEQ ID NOs: 216, 217 and 239 or 280, 281 and 239) or one or more of the light chain CDR sequences for AC_05091 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05091 (SEQ ID NOs: 216, 217 and 240 or 280, 281 and 240) or one or more of the light chain CDR sequences for AC_05093 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05093 (SEQ ID NOs: 216, 217 and 241 or 280, 281 and 241) or one or more of the light chain CDR sequences for AC_05094 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05094 (SEQ ID NOs: 216, 217 and 242 or 280, 281 and 242) or one or more of the light chain CDR sequences for AC_05096 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05096 (SEQ ID NOs: 216, 217 and 244 or 280, 281 and 244) or one or more of the light chain CDR sequences for AC_05097 (SEQ ID NOs: 90, 91 and 311) and one or more of the heavy chain CDR sequences for AC_05097 (SEQ ID NOs: 216, 217 and 245 or 280, 281 and 245) or one or more of the light chain CDR sequences for Fab1 (SEQ ID NOs: 90, 91 and 322) and one or more of the heavy chain CDR sequences for Fab1 (SEQ ID NOs: 248, 249 and 250 or 289, 290 and 250) or one or more of the light chain CDR sequences for Fab3 (SEQ ID NOs: 324, 325 and 326) and one or more of the heavy chain CDR sequences for Fab3 (SEQ ID NOs: 254, 255 and 256 or 293, 294 and 256). Most preferably, B2 comprises the CDRs and / or the VL and VH of AC_05088, AC_05090 / ffAC_05337, AC_05093, AC_05097, Fab1, and / or Fab3. In a preferred embodiment B2 comprises the CDRs and / or the VL and VH of ffAC_05337, i.e. the three heavy chain CDRs of SEQ ID NOs 216, 217 and 239 and three light chain CDRs of SEQ ID NOs: 90, 91, and 311, and / or the VL sequence of 430 and the VH sequence of SEQ ID NO: 431. As explained further in the Examples, the references to exemplary B2 polypeptides (such as “Fab1”) are nomenclature based on the libraries from which the particular binders were identified, and are not specific references to particular types, or fragments, of antibodies. To put another way, “Fab1” is not necessarily a Fab fragment. Accordingly, the CDRs, VL and VH amino acid sequences defined for each of the exemplary B2 polypeptides can be used in any compatible antibody format, or fragment thereof. Preferred CEA binding domains may comprise at least a heavy chain CDR3 as defined in any individual row of Table D(1a) and / or a light chain CDR3 as defined in in any individual row of Table D(2). Accordingly, in one embodiment binding domain B2 comprises all six CDR sequences for a given antibody (VH / VL) reference, for example binding domain B2 might comprise all six CDR sequences of an antibody selected from the list consisting of: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05080; AC_05081; AC_05082; AC_05083; AC_05084; AC_05085; AC_05086; AC_05087; AC_05088; AC_05089; AC_05090; AC_05091; AC_05092; AC_05093; AC_05094; AC_05095; AC_05096; AC_05097; AC_05098; AC_05099; AC_05100; Fab1; Fab2; Fab3; Fab4; Fab5; Fab6; Fab7; Fab8; Fab9; Fab10; Fab11; ffAC_05337 and mAb2, preferably: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05081; AC_05088; AC_05089; AC_05090; AC_05091; AC_05093; AC_05094; AC_05096; AC_05097; Fab1; ffAC_05337 and Fab3, most preferably AC_05088; AC_05090; the CEA binding domain of ffAC_05337; AC_05093; AC_05097; Fab1; and Fab3. In one embodiment, binding domain B2 comprises a VH and / or a VL amino acid sequence as given in Table B. In one embodiment, binding domain B2 comprises a VH and VL amino acid sequence as given in Table B for a particular antibody reference. For example, binding domain B2 may comprise the VH sequence of AC_05059 (SEQ ID NO: 33) and / or the VL sequence of AC_05059 (SEQ ID NO: 31) or binding domain B2 may comprise the VH sequence of AC_05060 (SEQ ID NO: 37) and / or the VL sequence of AC_05060 (SEQ ID NO: 35) or binding domain B2 may comprise the VH sequence of AC_05062 (SEQ ID NO: 45) and / or the VL sequence of AC_05062 (SEQ ID NO: 43) or binding domain B2 may comprise the VH sequence of AC_05064 (SEQ ID NO: 49) and / or the VL sequence of AC_05064 (SEQ ID NO: 47) or binding domain B2 may comprise the VH sequence of AC_05079 (SEQ ID NO: 53) and / or the VL sequence of AC_05079 (SEQ ID NO: 51) or binding domain B2 may comprise the VH sequence of AC_05081 (SEQ ID NO: 61) and / or the VL sequence of AC_05081 (SEQ ID NO: 59) or binding domain B2 may comprise the VH sequence of AC_05088 (SEQ ID NO: 122) and / or the VL sequence of AC_05088 (SEQ ID NO: 120) or binding domain B2 may comprise the VH sequence of AC_05089 (SEQ ID NO: 126) and / or the VL sequence of AC_05089 (SEQ ID NO: 124) or binding domain B2 may comprise the VH sequence of AC_05090 (SEQ ID NO: 130) and / or the VL sequence of AC_05090 (SEQ ID NO: 128) or binding domain B2 may comprise the VH sequence of AC_05091 (SEQ ID NO: 134) and / or the VL sequence of AC_05091 (SEQ ID NO: 132) or binding domain B2 may comprise the VH sequence of AC_05093 (SEQ ID NO: 142) and / or the VL sequence of AC_05093 (SEQ ID NO: 140) or binding domain B2 may comprise the VH sequence of AC_05094 (SEQ ID NO: 146) and / or the VL sequence of AC_05094 (SEQ ID NO: 144) or binding domain B2 may comprise the VH sequence of AC_05096 (SEQ ID NO: 154) and / or the VL sequence of AC_05096 (SEQ ID NO: 152) or binding domain B2 may comprise the VH sequence of AC_05097 (SEQ ID NO: 158) and / or the VL sequence of AC_05097 (SEQ ID NO: 156) or binding domain B2 may comprise the VH sequence of Fab1 (SEQ ID NO: 174) and / or the VL sequence of Fab1 (SEQ ID NO: 172) or binding domain B2 may comprise the VH sequence of Fab3 (SEQ ID NO: 182) and / or the VL sequence of Fab3 (SEQ ID NO: 180) or binding domain B2 may comprise the VH sequence of ffAC_05337 (SEQ ID NO: 433) and / or the VL sequence of ffAC_05337 (SEQ ID NO: 432). In one embodiment the CEA binding domain of B2 is selected from: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05080; AC_05081; AC_05082; AC_05083; AC_05084; AC_05085; AC_05086; AC_05087; AC_05088; AC_05089; AC_05090; AC_05091; AC_05092; AC_05093; AC_05094; AC_05095; AC_05096; AC_05097; AC_05098; AC_05099; AC_05100; Fab1; Fab2; Fab3; Fab4; Fab5; Fab6; Fab7; Fab8; Fab9; Fab10; Fab11; the CEA binding domain of ffAC_05337 and mAb2, preferably: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05081; AC_05088; AC_05089; AC_05090; AC_05091; AC_05093; AC_05094; AC_05096; AC_05097; Fab1; the CEA binding domain of ffAC_05337; and Fab3, most preferably AC_05088; AC_05090; the CEA binding domain of ffAC_05337; AC_05093; AC_05097; Fab1; and Fab3. Thus, the CDR or VH and VL sequences of binding domain B2 might be selected from antibodies from the group consisting of: (a) AC_05059 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 31; VH: SEQ ID NO: 33) (b) AC_05060 (heavy chain CDRs: SEQ ID NOs: 219, 220 and 221 or 282, 283 and 221; light chain CDRs: SEQ ID NOs: 312, 91 and 313; VL: SEQ ID NO: 35; VH: SEQ ID NO: 37) (c) AC_05061 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 224 or 284, 285 and 224; light chain CDRs: SEQ ID NOs: 90, 91 and 314; VL: SEQ ID NO: 39; VH: SEQ ID NO: 41) (d) AC_05062 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 225 or 284, 285 and 225; light chain CDRs: SEQ ID NOs: 315, 316 and 94; VL: SEQ ID NO: 43; VH: SEQ ID NO: 45) (e) AC_05064 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 226 or 284, 285 and 226; light chain CDRs: SEQ ID NOs: 90, 91 and 317; VL: SEQ ID NO: 47; VH: SEQ ID NO: 49) (f) AC_05079 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 227 or 280, 281 and 227; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 51; VH: SEQ ID NO: 53) (g) AC_05080 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 228 or 280, 281 and 228; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 55; VH: SEQ ID NO: 57) (h) AC_05081 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 229 or 280, 281 and 229; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 59; VH: SEQ ID NO: 61) (i) AC_05082 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 230 or 284, 285 and 230; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 63; VH: SEQ ID NO: 65) (j) AC_05083 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 231 or 284, 285 and 231; light chain CDRs: SEQ ID NOs: 318, 91 and 319; VL: SEQ ID NO: 67; VH: SEQ ID NO: 69) (k) AC_05084 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 232 or 284, 285 and 232; light chain CDRs: SEQ ID NOs: 90, 91 and 320; VL: SEQ ID NO: 71; VH: SEQ ID NO: 106) (l) AC_05085 (heavy chain CDRs: SEQ ID NOs: 219, 233 and 234 or 286, 287 and 234; light chain CDRs: SEQ ID NOs: 90, 91 and 311 ; VL: SEQ ID NO: 108; VH: SEQ ID NO: 110) (m) AC_05086 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 235 or 280, 281 and 235; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 112; VH: SEQ ID NO: 114) (n) AC_05087 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 236 or 280, 281 and 236; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 116; VH: SEQ ID NO: 118) (o) AC_05088 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 237 or 280, 281 and 237; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 120; VH: SEQ ID NO: 122) (p) AC_05089 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 238 or 280, 281 and 238; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 124; VH: SEQ ID NO: 126) (q) AC_05090 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 239 or 280, 281 and 239; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 128; VH: SEQ ID NO: 130) (r) AC_05091 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 240 or 280, 281 and 240; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 132; VH: SEQ ID NO: 134) (s) AC_05092 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218; light chain CDRs: SEQ ID NOs: 321, 91 and 311; VL: SEQ ID NO: 136; VH: SEQ ID NO: 138) (t) AC_05093 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 241 or 280, 281 and 241; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 140; VH: SEQ ID NO: 142) (u) AC_05094 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 242 or 280, 281 and 242; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 144; VH: SEQ ID NO: 146) (v) AC_05095 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 243 or 280, 281 and 243; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 148; VH: SEQ ID NO: 150) (w) AC_05096 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 244 or 280, 281 and 244; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 152; VH: SEQ ID NO: 154) (x) AC_05097 (heavy chain CDRs: SEQ ID NOs: 217, 216 and 245 or 280, 281 and 245; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 156; VH: SEQ ID NO: 158) (y) AC_05098 (heavy chain CDRs: SEQ ID NOs: 219, 220 and 246 or 282, 283 and 246; light chain CDRs: SEQ ID NOs: 312, 91 and 313; VL: SEQ ID NO: 160; VH: SEQ ID NO: 162) (z) AC_05099 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 224 or 288, 285 and 224; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 164; VH: SEQ ID NO: 166) (aa) AC_05100 (heavy chain CDRs: SEQ ID NOs: 222, 223 and 247 or 288, 285 and 247; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 168; VH: SEQ ID NO: 170) (ab) Fab1 (heavy chain CDRs: SEQ ID NOs: 248, 249 and 250 or 289, 290 and 250; light chain CDRs: SEQ ID NOs: 90, 91 and 322; VL: SEQ ID NO: 172; VH: SEQ ID NO: 174) (ac) Fab2 (heavy chain CDRs: SEQ ID NOs: 251, 252 and 253 or 291, 292 and 253; light chain CDRs: SEQ ID NOs: 90, 91 and 323; VL: SEQ ID NO: 176; VH: SEQ ID NO: 178) (ad) Fab3 (heavy chain CDRs: SEQ ID NOs: 254, 255 and 256 or 293, 294 and 256; light chain CDRs: SEQ ID NOs: 324, 325 and 326; VL: SEQ ID NO: 180; VH: SEQ ID NO: 182) (ae) Fab4 (heavy chain CDRs: SEQ ID NOs: 257, 258 and 259 or 295, 296 and 259; light chain CDRs: SEQ ID NOs: 90, 91 and 327; VL: SEQ ID NO: 184; VH: SEQ ID NO: 186) (af) Fab5 (heavy chain CDRs: SEQ ID NOs: 260, 261 and 262 or 297, 298 and 262; light chain CDRs: SEQ ID NOs: 324, 325 and 328; VL: SEQ ID NO: 188; VH: SEQ ID NO: 190) (ag) Fab6 (heavy chain CDRs: SEQ ID NOs: 263, 264 and 265 or 299, 300 and 265; light chain CDRs: SEQ ID NOs: 324, 325 and 329; VL: SEQ ID NO: 192; VH: SEQ ID NO: 194) (ah) Fab7 (heavy chain CDRs: SEQ ID NOs: 266, 267 and 268 or 301, 302 and 268; light chain CDRs: SEQ ID NOs: 90, 91 and 330; VL: SEQ ID NO: 196; VH: SEQ ID NO: 198) (ai) Fab8 (heavy chain CDRs: SEQ ID NOs: 269, 270 and 271 or 303, 304 and 271; light chain CDRs: SEQ ID NOs: 90, 91 and 331; VL: SEQ ID NO: 200; VH: SEQ ID NO: 202) (aj) Fab9 (heavy chain CDRs: SEQ ID NOs: 272, 335 and 273 or 305, 306 and 273; light chain CDRs: SEQ ID NOs: 90, 91 and 332; VL: SEQ ID NO: 204; VH: SEQ ID NO: 206) (ak) Fab10 (heavy chain CDRs: SEQ ID NOs: 274, 275 and 276 or 307, 308 and 276; light chain CDRs: SEQ ID NOs: 90, 91 and 333; VL: SEQ ID NO: 208; VH: SEQ ID NO: 210) (al) Fab11 (heavy chain CDRs: SEQ ID NOs: 277, 278 and 279 or 309, 310 and 279; light chain CDRs: SEQ ID NOs: 324, 325 and 334; VL: SEQ ID NO: 212; VH: SEQ ID NO: 214) and / or (am) ffAC_05337 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 239; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 432; VH: SEQ ID NO: 433), preferably (am) ffAC_05337 (heavy chain CDRs: SEQ ID NOs: 216, 217 and 239; light chain CDRs: SEQ ID NOs: 90, 91 and 311; VL: SEQ ID NO: 432; VH: SEQ ID NO: 433),. The numbering of the antibody (e.g. Antibody X / Y) defines the heavy chain variable region (X) and the light chain variable region (Y), respectively (or, where a single number is indicated, the heavy chain variable region [X] only is defined). As described above, the sequences may be one or more CDR sequence, or the VH and / or VL sequence. As described above, the sequences of the bispecific polypeptide may comprise specified mutations. A variant of any one of the heavy or light chain amino acid sequences or CDR sequences recited herein may be a substitution, deletion or addition variant of said sequence. A variant may comprise 1, 2, 3, 4, 5, up to 10, up to 20, up to 30 or more amino acid substitutions and / or deletions from the said sequence. “Deletion” variants may comprise the deletion of individual amino acids, deletion of small groups of amino acids such as 2, 3, 4 or 5 amino acids, or deletion of larger amino acid regions, such as the deletion of specific amino acid domains or other features. "Substitution" variants preferably involve the replacement of one or more amino acids with the same number of amino acids and making conservative amino acid substitutions. For example, an amino acid may be substituted with an alternative amino acid having similar properties, for example, another basic amino acid, another acidic amino acid, another neutral amino acid, another charged amino acid, another hydrophilic amino acid, another hydrophobic amino acid, another polar amino acid, another aromatic amino acid or another aliphatic amino acid. Some properties of the 20 main amino acids which can be used to select suitable substituents are as follows: Ala, A aliphatic, hydrophobic, neutral Met, M hydrophobic, neutral Cys, C polar, hydrophobic, neutral Asn, N polar, hydrophilic, neutral Asp, D polar, hydrophilic, charged (-) Pro, P hydrophobic, neutral Glu, E polar, hydrophilic, charged (-) Gln, Q polar, hydrophilic, neutral Phe, F aromatic, hydrophobic, neutral Arg, R polar, hydrophilic, charged (+) Gly, G aliphatic, neutral Ser, S polar, hydrophilic, neutral His, H aromatic, polar, hydrophilic, charged (+) Thr, T polar, hydrophilic, neutral Ile, I aliphatic, hydrophobic, neutral Val, V aliphatic, hydrophobic, neutral Lys, K polar, hydrophilic, charged (+) Trp, W aromatic, hydrophobic, neutral Leu, L aliphatic, hydrophobic, neutral Tyr, Y aromatic, polar, hydrophobic Amino acids herein may be referred to by full name, three letter code or single letter code. Preferred "derivatives" or "variants" include those in which instead of the naturally occurring amino acid the amino acid which appears in the sequence is a structural analog thereof. Amino acids used in the sequences may also be derivatised or modified, e.g. labelled, providing the function of the polypeptide is not significantly adversely affected. Derivatives and variants as described above may be prepared during synthesis of the polypeptide or by post-production modification, or when the polypeptide is in recombinant form using the known techniques of site-directed mutagenesis, random mutagenesis, or enzymatic cleavage and / or ligation of nucleic acids. Preferably variants have an amino acid sequence which has more than 60%, or more than 70%, e.g. 75 or 80%, preferably more than 85%, e.g. more than 90 or 95% amino acid identity to a sequence as shown in the sequences disclosed herein. This level of amino acid identity may be seen across the full length of the relevant SEQ ID NO sequence or over a part of the sequence, such as across 20, 30, 50, 75, 100, 150, 200 or more amino acids, depending on the size of the full-length polypeptide. In one embodiment binding domain B2 is specific for CEA, typically human CEA and may comprise any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which consists of the sequence: “G, F, T, F, S, S, S, Y” or which comprises the consensus sequence of: “G, F, T, F, G / S, S, Y, Y / A”; (b) a heavy chain CDR2 sequence which consists of the sequence: “I, G, S, G, S, Y, S, T” or which comprises the consensus sequence of: “I, S, G, Y / S, G, Y / G, S, T”; (c) a heavy chain CDR3 sequence which comprises the consensus sequence of: “A, R, Y, P, S, V, P / L, F, P, Q, S, P / H / L, H / P / L, L / F / V / W, D, Y” or which comprises the consensus sequence of: “A, R, H / Y, G, Y, G / S / T, V / H, L / F, D, Y”; (d) a light chain CDR1 sequence which consists of the sequence: “Q, S, I, S, S, Y” or which comprises the consensus sequence of: “Q, S, I, R / S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which consists of the sequence: “Q, Q, A, G, N, P, H, T” or which comprises the consensus sequence of: “Q, Q, G / Y, T / P / A, W / -, Y / -, F / V, P, F / Y, T”. In an alternative embodiment binding domain B2 is specific for CEA, typically human CEA and may comprise any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which consists of the sequence: “G, F, T, F, S, S, S, Y”; (b) a heavy chain CDR2 sequence which consists of the sequence: “I, G, S, G, S, Y, S, T”; (c) a heavy chain CDR3 sequence which comprises the consensus sequence of: “A, R, Y, P, S, V, P / L, F, P, Q, S, P / H / L, H / P / L, L / F / V / W, D, Y”; (d) a light chain CDR1 sequence which consists of the sequence: “Q, S, I, S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which consists of the sequence: “Q, Q, A, G, N, P, H, T”. Binding domain B2 may comprise at least a heavy chain CDR3 as defined in (c) of this embodiment and / or a light chain CDR3 as defined in (f). Binding domain B2 may comprise all three heavy chain CDR sequences of (a), (b) and (c) and / or all three light chain CDR sequences of (d), (e) and (f). In a further alternative embodiment binding domain B2 is specific for CEA, typically human CEA and may comprise any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which comprises the consensus sequence of: “G, F, T, F, G / S, S, Y, Y / A”; (b) a heavy chain CDR2 sequence which comprises the consensus sequence of: “I, S, G, Y / S, G, Y / G, S, T”; (c) a heavy chain CDR3 sequence which comprises the consensus sequence of: “A, R, H / Y, G, Y, G / S / T, V / H, L / F, D, Y”; (d) a light chain CDR1 sequence which comprises the consensus sequence of: “Q, S, I, R / S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which comprises the consensus sequence of: “Q, Q, G / Y, T / P / A, W / -, Y / -, F / V, P, F / Y, T”. Binding domain B2 may comprise at least a heavy chain CDR3 as defined in (c) of this embodiment and / or a light chain CDR3 as defined in (f). Binding domain B2 may comprise all three heavy chain CDR sequences of (a), (b) and (c) and / or all three light chain CDR sequences of (d), (e) and (f). Examples of complete heavy and light chain variable region amino acid sequences for binding domain B2 are shown in Table B. Exemplary nucleic acid sequences encoding each amino acid sequence are also shown. The numbering of said VH and VL regions in Table B corresponds to the numbering system used as in Table D(1a), Table D(1b) and / or Table D(2). Thus, for example, the amino acid sequence for “AC_05088, light chain VL” is an example of a complete VL region sequence comprising all three CDRs of VL number AC_05088 shown in Table D(2)and the amino acid sequence for “AC_05088, heavy chain VH” is an example of a complete VH region sequence comprising all three CDRs of VH number AC_05088 shown in Table D(1a) and / or Table D(1b). In exemplary embodiments, binding domain B2 comprises: (a) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05059 (SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218 and / or SEQ ID NOs: 90, 91 and 311) (b) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05060 (SEQ ID NOs: 219, 220 and 221 or 282, 283 and 221 and / or SEQ ID NOs: 312, 91 and 313) (c) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05061 (SEQ ID NOs: 222, 223 and 224 or 284, 285 and 224 and / or SEQ ID NOs: 90, 91 and 314) (d) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05062 (SEQ ID NOs: 222, 223 and 225 or 284, 285 and 225 and / or SEQ ID NOs: 315, 316 and 94) (e) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05064 (SEQ ID NOs: 222, 223 and 226 or 284, 285 and 226 and / or SEQ ID NOs: 90, 91 and 317) (f) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05079 (SEQ ID NOs: 216, 217 and 227 or 280, 281 and 227 and / or SEQ ID NOs: 90, 91 and 311) (g) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05080 (SEQ ID NOs: 216, 217 and 228 or 280, 281 and 228 and / or SEQ ID NOs: 90, 91 and 311) (h) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05081 (SEQ ID NOs: 216, 217 and 229 or 280, 281 and 229 and / or SEQ ID NOs: 90, 91 and 311) (i) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05082 (SEQ ID NOs: 222, 223 and 230 or 284, 285 and 230 and / or SEQ ID NOs: 90, 91 and 311) (j) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05083 (SEQ ID NOs: 222, 223 and 231 or 284, 285 and 231 and / or SEQ ID NOs: 318, 91 and 319) (k) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05084 (SEQ ID NOs: 222, 223 and 232 or 284, 285 and 232 and / or SEQ ID NOs: 90, 91 and 320) (l) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05085 (SEQ ID NOs: 219, 233 and 234 or 286, 287 and 234 and / or SEQ ID NOs: 90, 91 and 311) (m) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05086 (SEQ ID NOs: 216, 217 and 235 or 280, 281 and 235 and / or SEQ ID NOs: 90, 91 and 311) (n) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05087 (SEQ ID NOs: 216, 217 and 236 or 280, 281 and 236 and / or SEQ ID NOs: 90, 91 and 311) (o) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05088 (SEQ ID NOs: 216, 217 and 237 or 280, 281 and 237 and / or SEQ ID NOs: 90, 91 and 311) (p) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05089 (SEQ ID NOs: 216, 217 and 238 or 280, 281 and 238 and / or SEQ ID NOs: 90, 91 and 311) (q) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05090 / ffAC_05337 (SEQ ID NOs: 216, 217 and 239 or 280, 281 and 239 and / or SEQ ID NOs: 90, 91 and 311) (r) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05091 (SEQ ID NOs: 216, 217 and 240 or 280, 281 and 240 and / or SEQ ID NOs: 90, 91 and 311) (s) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05092 (SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218 and / or SEQ ID NOs: 321, 91 and 311) (t) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05093 (SEQ ID NOs: 216, 217 and 241 or 280, 281 and 241 and / or SEQ ID NOs: 90, 91 and 311) (u) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05094 (SEQ ID NOs: 216, 217 and 242 or 280, 281 and 242 and / or SEQ ID NOs: 90, 91 and 311) (v) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05095 (SEQ ID NOs: 216, 217 and 243 or 280, 281 and 243 and / or SEQ ID NOs: 90, 91 and 311) (w) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05096 (SEQ ID NOs: 216, 217 and 244 or 280, 281 and 244 and / or SEQ ID NOs: 90, 91 and 311) (x) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05097 (SEQ ID NOs: 217, 216 and 245 or 280, 281 and 245 and / or SEQ ID NOs: 90, 91 and 311) (y) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05098 (SEQ ID NOs: 219, 220 and 246 or 282, 283 and 246 and / or SEQ ID NOs: 312, 91 and 313) (z) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05099 (SEQ ID NOs: 222, 223 and 224 or 288, 285 and 224 and / or SEQ ID NOs: 90, 91 and 311) (aa) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05100 (SEQ ID NOs: 222, 223 and 247 or 288, 285 and 247 and / or SEQ ID NOs: 90, 91 and 311) (ab) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab1 (SEQ ID NOs: 248, 249 and 250 or 289, 290 and 250 and / or SEQ ID NOs: 90, 91 and 322) (ac) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab2 (SEQ ID NOs: 251, 252 and 253 or 291, 292 and 253 and / or SEQ ID NOs: 90, 91 and 323) (ad) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab3 (SEQ ID NOs: 254, 255 and 256 or 293, 294 and 256 and / or SEQ ID NOs: 324, 325 and 326) (ae) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab4 (SEQ ID NOs: 257, 258 and 259 or 295, 296 and 259 and / or SEQ ID NOs: 90, 91 and 327) (af) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab5 (SEQ ID NOs: 260, 261 and 262 or 297, 298 and 262 and / or SEQ ID NOs: 324, 325 and 328) (ag) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab6 (SEQ ID NOs: 263, 264 and 265 or 299, 300 and 265 and / or SEQ ID NOs: 324, 325 and 329) (ah) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab7 (SEQ ID NOs: 266, 267 and 268 or 301, 302 and 268 and / or SEQ ID NOs: 90, 91 and 330) (ai) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab8 (SEQ ID NOs: 269, 270 and 271 or 303, 304 and 271 and / or SEQ ID NOs: 90, 91 and 331) (aj) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab9 (SEQ ID NOs: 272, 335 and 273 or 305, 306 and 273 and / or SEQ ID NOs: 90, 91 and 332) (ak) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab10 (SEQ ID NOs: 274, 275 and 276 or 307, 308 and 276 and / or SEQ ID NOs: 90, 91 and 333) and / or (al) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab11 (SEQ ID NOs: 277, 278 and 279 or 309, 310 and 279 and / or SEQ ID NOs: 324, 325 and 334). Thus, binding domain B2 may comprise: (a) the heavy chain variable region and / or the light chain variable region of antibody AC_05059 (SEQ ID NO: 33 and / or SEQ ID NO: 31) (b) the heavy chain variable region and / or the light chain variable region antibody AC_05060 (SEQ ID NO: 37 and / or SEQ ID NO: 35) (c) the heavy chain variable region and / or the light chain variable region of antibody AC_05061 (SEQ ID NO: 41 and / or SEQ ID NO: 39) (d) the heavy chain variable region and / or the light chain variable region of antibody AC_05062 (SEQ ID NO: 45 and / or SEQ ID NO: 43) (e) the heavy chain variable region and / or the light chain variable region of antibody AC_05064 (SEQ ID NO: 49 and / or SEQ ID NO: 47) (f) the heavy chain variable region and / or the light chain variable region of antibody AC_05079 (SEQ ID NO: 53 and / or SEQ ID NO: 51) (g) the heavy chain variable region and / or the light chain variable region of antibody AC_05080 (SEQ ID NO: 57 and / or SEQ ID NO: 55) (h) the heavy chain variable region and / or the light chain variable region antibody AC_05081 (SEQ ID NO: 61 and / or SEQ ID NO: 59) (i) the heavy chain variable region and / or the light chain variable region of antibody AC_05082 (SEQ ID NO: 65 and / or SEQ ID NO: 63) (j) the heavy chain variable region and / or the light chain variable region antibody AC_05083 (SEQ ID NO: 69 and / or SEQ ID NO: 67) (k) the heavy chain variable region and / or the light chain variable region of antibody AC_05084 (SEQ ID NO: 106 and / or SEQ ID NO: 71) (l) the heavy chain variable region and / or the light chain variable region antibody AC_05085 (SEQ ID NO: 110 and / or SEQ ID NO: 108) (m) the heavy chain variable region and / or the light chain variable region of antibody AC_05086 (SEQ ID NO: 114 and / or SEQ ID NO: 112) (n) the heavy chain variable region and / or the light chain variable region of antibody AC_05087 (SEQ ID NO: 118 and / or SEQ ID NO: 116) (o) the heavy chain variable region and / or the light chain variable region of antibody AC_05088 (SEQ ID NO: 122 and / or SEQ ID NO: 120) (p) the heavy chain variable region and / or the light chain variable region of antibody AC_05089 (SEQ ID NO: 126 and / or SEQ ID NO: 124) (q) the heavy chain variable region and / or the light chain variable region of antibody AC_05090 (SEQ ID NO: 130 and / or SEQ ID NO: 128) (r) the heavy chain variable region and / or the light chain variable region antibody AC_05091 (SEQ ID NO: 134 and / or SEQ ID NO: 132) (s) the heavy chain variable region and / or the light chain variable region of antibody AC_05092 (SEQ ID NO: 138 and / or SEQ ID NO: 136) (t) the heavy chain variable region and / or the light chain variable region of antibody AC_05093 (SEQ ID NO: 142 and / or SEQ ID NO: 140) (u) the heavy chain variable region and / or the light chain variable region of antibody AC_05094 (SEQ ID NO: 146 and / or SEQ ID NO: 144) (v) the heavy chain variable region and / or the light chain variable region of antibody AC_05095 (SEQ ID NO: 150 and / or SEQ ID NO: 148) (w) the heavy chain variable region and / or the light chain variable region of antibody AC_05096 (SEQ ID NO: 154 and / or SEQ ID NO: 152) (x) the heavy chain variable region and / or the light chain variable region antibody AC_05097 (SEQ ID NO: 158 and / or SEQ ID NO: 156) (y) the heavy chain variable region and / or the light chain variable region of antibody AC_05098 (SEQ ID NO: 162 and / or SEQ ID NO: 160) (z) the heavy chain variable region and / or the light chain variable region antibody AC_05099 (SEQ ID NO: 166 and / or SEQ ID NO: 164) (aa) the heavy chain variable region and / or the light chain variable region of antibody AC_05100 (SEQ ID NO: 170 and / or SEQ ID NO: 168) (ab) the heavy chain variable region and / or the light chain variable region of antibody Fab1 (SEQ ID NO: 174 and / or SEQ ID NO: 172) (ac) the heavy chain variable region and / or the light chain variable region of antibody Fab2 (SEQ ID NO: 178 and / or SEQ ID NO: 176) (ad) the heavy chain variable region and / or the light chain variable region of antibody Fab3 (SEQ ID NO: 182 and / or SEQ ID NO: 180) (ae) the heavy chain variable region and / or the light chain variable region of antibody Fab4 (SEQ ID NO: 186 and / or SEQ ID NO: 184) (af) the heavy chain variable region and / or the light chain variable region of antibody Fab5 (SEQ ID NO: 190 and / or SEQ ID NO: 188) (ag) the heavy chain variable region and / or the light chain variable region of antibody Fab6 (SEQ ID NO: 194 and / or SEQ ID NO: 192) (ah) the heavy chain variable region and / or the light chain variable region of antibody Fab7 (SEQ ID NO: 198 and / or SEQ ID NO: 196) (ai) the heavy chain variable region and / or the light chain variable region of antibody Fab8 (SEQ ID NO: 202 and / or SEQ ID NO: 200) (aj) the heavy chain variable region and / or the light chain variable region of antibody Fab9 (SEQ ID NO: 206 and / or SEQ ID NO: 204) (ak) the heavy chain variable region and / or the light chain variable region of antibody Fab10 (SEQ ID NO: 210 and / or SEQ ID NO: 208) (al) the heavy chain variable region and / or the light chain variable region of antibody Fab11 (SEQ ID NO: 214 and / or SEQ ID NO: 212) (am) the heavy chain variable region and / or the light chain variable region of antibody mAb2 (SEQ ID NO: 387 and / or SEQ ID NO: 385) and / or (an) the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NO: 433 and / or SEQ ID NO: 432). In one embodiment, binding domain B2 may comprise: (a) the light chain and / or the heavy chain of antibody AC_05059 (SEQ ID NO: 388 and / or SEQ ID NO: 389) (b) the light chain and / or the heavy chain of antibody AC_05060 (SEQ ID NO: 390 and / or SEQ ID NO: 391) (c) the light chain and / or the heavy chain of antibody AC_05061 (SEQ ID NO: 392 and / or (SEQ ID NO: 393) (d) the light chain and / or the heavy chain of antibody AC_05062 (SEQ ID NO: 394 and / or SEQ ID NO: 395) (e) the light chain and / or the heavy chain of antibody AC_05064 (SEQ ID NO: 396 and / or SEQ ID NO: 397) (f) the light chain and / or the heavy chain of antibody AC_05079 (SEQ ID NO: 398 and / or SEQ ID NO: 399) (g) the light chain and / or the heavy chain of antibody AC_05081 (SEQ ID NO: 400 and / or SEQ ID NO: 401) (h) the light chain and / or the heavy chain of antibody AC_05088 (SEQ ID NO: 402 and / or SEQ ID NO: 403) (i) the light chain and / or the heavy chain of antibody AC_05089 (SEQ ID NO: 404 and / or SEQ ID NO: 405) (j) the light chain and / or the heavy chain of antibody AC_05090 (SEQ ID NO: 406 and / or SEQ ID NO: 407) (k) the light chain and / or the heavy chain of antibody AC_05091 (SEQ ID NO: 408 and / or SEQ ID NO: 409) (l) the light chain and / or the heavy chain of antibody AC_05093 (SEQ ID NO: 410 and / or SEQ ID NO: 411) (m) the light chain and / or the heavy chain of antibody AC_05094 (SEQ ID NO: 412 and / or SEQ ID NO: 413) (n) the light chain and / or the heavy chain of antibody AC_05096 (SEQ ID NO: 414 and / or SEQ ID NO: 415) (o) the light chain and / or the heavy chain of antibody AC_05097 (SEQ ID NO: 416 and / or SEQ ID NO: 417) (p) the light chain and / or the heavy chain of antibody Fab1 (SEQ ID NO: 418 and / or SEQ ID NO: 419) and / or (q) the light chain and / or the heavy chain of antibody Fab3 (SEQ ID NO: 420 and / or (SEQ ID NO: 421). It will be appreciated by the skilled person, and it is included herein, that mutations described herein for the RUBYTMformat and / or the optimised RUBYTMformat can be applied to the above light chain and / or the heavy chain sequences of the binding domain B2. In one embodiment binding domain B2 may comprise one or more variants of the above-defined light chain variable regions and / or said heavy chain variable regions (and / or light chain and / or heavy chain) having at least 90% sequence identity thereto or 95% sequence identity thereto or 99% sequence identity thereto. Binding domain B2 may also comprise variants of the CDR sequences specified herein, for example variants where up one, two, three, four or five amino acid residues are substituted, deleted to added compared to the specified reference sequences. In one embodiment the CEA binding domain of B2 is selected from: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05080; AC_05081; AC_05082; AC_05083; AC_05084; AC_05085; AC_05086; AC_05087; AC_05088; AC_05089; AC_05090; AC_05091; AC_05092; AC_05093; AC_05094; AC_05095; AC_05096; AC_05097; AC_05098; AC_05099; CEA binding domain of ffAC_05337 and AC_05100; Fab1; Fab2; Fab3; Fab4; Fab5; Fab6; Fab7; Fab8; Fab9; Fab10; Fab11; and mAb2, preferably: AC_05059; AC_05060; AC_05061; AC_05062; AC_05064; AC_05079; AC_05081; AC_05088; AC_05089; AC_05090; AC_05091; AC_05093; AC_05094; AC_05096; and AC_05097; Fab1; and Fab3, most preferably AC_05088; AC_05090; AC_05093; and AC_05097; Fab1; the CEA binding domain of ffAC_05337 and Fab3. The CDRs, VL, VH, light chain and / or heavy chain of the above antibodies as described in the first aspect of the invention are relevant to, and included in, the second aspect of the invention. Advantageously, binding domain B2 binds to human CEA with a KD of less than 2x10-6M or less than 1.5x10-7M or less than 1.5x10-8M or less than 2.5x10-8M or less than 4.5x10-8M or less than 5.5x10-8M or less than 6.5x10-9M or less than 2.5x10-9M or less than 2x10-9M or less than 9.5x10-10M or less than 4.5x10-10M or less than 7.5x10-11M or less than 8.5x10-12M or less than 1.5x10-12M or less than 1x10-12M, preferably less than 1.5x10-8M or less than 2.5x10-9M or less than 1.5x10-12M. Preferably, the KD is measured in Octet; for example, as explained in the Examples. Preferably, the KD is measured in Octet; for example, as explained in the Examples. In a preferred embodiment, the bispecific polypeptide is a bispecific antibody, such as a bispecific antibody in the RUBYTMformat or optimised RUBYTMformat, as both described herein. Exemplary CD40–CEA bispecific antibodies In one embodiment of the bispecific polypeptides, binding domain B1 is an IgG and binding domain B2 is an scFv. Conversely, binding domain B1 may be an scFv and binding domain B2 may be an IgG. In one embodiment binding domain B1 is an immunoglobulin and binding domain B2 is a Fab. Conversely, binding domain B1 may be a Fab and binding domain B2 may be an immunoglobulin. The bispecific polypeptide may optionally be in the RUBY™ format or optimised RUBY™ format, as both described herein. The bispecific polypeptide format is as described above and as laid out in Figure 23, and the bispecific polypeptide may comprise certain mutations as described above. In an embodiment, the bispecific polypeptide may comprise the CDRs of the light chains of any of the B1 domains described above (as laid out in Table C(2) below), and / or the CDRs of the heavy chains of any of the B1 domains described above (as laid out in Table C(1) below), in combination with any of the CDRs of the light chains of any of the B2 domains described above (as laid out in Table D(2)), and / or the CDRs of the heavy chains of any of the B2 domains described above (as laid out in Table D(1a) and / or Table D(1b)). In a preferred embodiment the bispecific polypeptide comprises the CDR sequences of ATOR-4066 (also referred to as ffAC_05337 herein), as follows: (a) binding domain B1 comprises three heavy chain CDRs of SEQ ID NOs: 81, 82 and 83 and three light chain CDRs of SEQ ID NOs: 96, 97, and 98; (b) binding domain B2 comprises three heavy chain CDRs of SEQ ID NOs 216, 217 and 239 and three light chain CDRs of SEQ ID NOs: 90, 91, and 311. In an embodiment, the bispecific polypeptide may comprise the light chain variable regions of any of the B1 domains described above (as laid out in Table A below), and / or the heavy chain variable regions of any of the B1 domains described above (as laid out in Table A below), in combination with any of the light chain variable regions of any of the B2 domains described above (as laid out in Table B), and / or the heavy chain variable regions of any of the B2 domains described above (as laid out in Table B). Thus, in certain embodiments B1 and B2 comprise the respective variable regions comprising the CDRs identified above. For example, B1 may comprise the heavy chain variable region and / or the light chain variable region of antibody G12 (SEQ ID NO: 19 and / or SEQ ID NO: 17) or G12_mut (SEQ ID NO: 29 and / or SEQ ID NO: 17) and B2 may comprise the heavy chain variable region and / or the light chain variable region of any of the reference CEA antibodies: (a) the heavy chain variable region and / or the light chain variable region of antibody AC_05059 (SEQ ID NO: 33 and / or SEQ ID NO: 31) (b) the heavy chain variable region and / or the light chain variable region of antibody AC_05060 (SEQ ID NO: 37 and / or SEQ ID NO: 35) (c) the heavy chain variable region and / or the light chain variable region of antibody AC_05061 (SEQ ID NO: 41 and / or SEQ ID NO: 39) (d) the heavy chain variable region and / or the light chain variable region of antibody AC_05062 (SEQ ID NO: 45 and / or SEQ ID NO: 43) (e) the heavy chain variable region and / or the light chain variable region of antibody AC_05064 (SEQ ID NO: 49 and / or SEQ ID NO: 47) (f) the heavy chain variable region and / or the light chain variable region of antibody AC_05079 (SEQ ID NO: 53 and / or SEQ ID NO: 51) (g) the heavy chain variable region and / or the light chain variable region of antibody AC_05080 (SEQ ID NO: 57 and / or SEQ ID NO: 55) (h) the heavy chain variable region and / or the light chain variable region of antibody AC_05081 (SEQ ID NO: 61 and / or SEQ ID NO: 59) (i) the heavy chain variable region and / or the light chain variable region of antibody AC_05082 (SEQ ID NO: 65 and / or SEQ ID NO: 63) (j) the heavy chain variable region and / or the light chain variable region of antibody AC_05083 (SEQ ID NO: 69 and / or SEQ ID NO: 67) (k) the heavy chain variable region and / or the light chain variable region of antibody AC_05084 (SEQ ID NO: 106 and / or SEQ ID NO: 71) (l) the heavy chain variable region and / or the light chain variable region of antibody AC_05085 (SEQ ID NO: 110 and / or SEQ ID NO: 108) (m) the heavy chain variable region and / or the light chain variable region of antibody AC_05086 (SEQ ID NO: 114 and / or SEQ ID NO: 112) (n) the heavy chain variable region and / or the light chain variable region of antibody AC_05087 (SEQ ID NO: 118 and / or SEQ ID NO: 116) (o) the heavy chain variable region and / or the light chain variable region of antibody AC_05088 (SEQ ID NO: 122 and / or SEQ ID NO: 120) (p) the heavy chain variable region and / or the light chain variable region of antibody AC_05089 (SEQ ID NO: 126 and / or SEQ ID NO: 124) (q) the heavy chain variable region and / or the light chain variable region of antibody AC_05090 (SEQ ID NO: 130 and / or SEQ ID NO: 128) (r) the heavy chain variable region and / or the light chain variable region of antibody AC_05091 (SEQ ID NO: 134 and / or SEQ ID NO: 132) (s) the heavy chain variable region and / or the light chain variable region of antibody AC_05092 (SEQ ID NO: 138 and / or SEQ ID NO: 136) (t) the heavy chain variable region and / or the light chain variable region of antibody AC_05093 (SEQ ID NO: 142 and / or SEQ ID NO: 140) (u) the heavy chain variable region and / or the light chain variable region of antibody AC_05094 (SEQ ID NO: 146 and / or SEQ ID NO: 144) (v) the heavy chain variable region and / or the light chain variable region of antibody AC_05095 (SEQ ID NO: 150 and / or SEQ ID NO: 148) (w) the heavy chain variable region and / or the light chain variable region of antibody AC_05096 (SEQ ID NO: 154 and / or SEQ ID NO: 152) (x) the heavy chain variable region and / or the light chain variable region of antibody AC_05097 (SEQ ID NO: 158 and / or SEQ ID NO: 156) (y) the heavy chain variable region and / or the light chain variable region of antibody AC_05098 (SEQ ID NO: 162 and / or SEQ ID NO: 160) (z) the heavy chain variable region and / or the light chain variable region of antibody AC_05099 (SEQ ID NO: 166 and / or SEQ ID NO: 164) (aa) the heavy chain variable region and / or the light chain variable region of antibody AC_05100 (SEQ ID NO: 170 and / or SEQ ID NO: 168) (ab) the heavy chain variable region and / or the light chain variable region of antibody Fab1 (SEQ ID NO: 174 and / or SEQ ID NO: 172) (ac) the heavy chain variable region and / or the light chain variable region of antibody Fab2 (SEQ ID NO: 178 and / or SEQ ID NO: 176) (ad) the heavy chain variable region and / or the light chain variable region antibody Fab3 (SEQ ID NO: 182 and / or SEQ ID NO: 180) (ae) the heavy chain variable region and / or the light chain variable region of antibody Fab4 (SEQ ID NO: 186 and / or SEQ ID NO: 184) (af) the heavy chain variable region and / or the light chain variable region of antibody Fab5 (SEQ ID NO: 190 and / or SEQ ID NO: 188) (ag) the heavy chain variable region and / or the light chain variable region of antibody Fab6 (SEQ ID NO: 194 and / or SEQ ID NO: 192) (ah) the heavy chain variable region and / or the light chain variable region of antibody Fab7 (SEQ ID NO: 198 and / or SEQ ID NO: 196) (ai) the heavy chain variable region and / or the light chain variable region of antibody Fab8 (SEQ ID NO: 202 and / or SEQ ID NO: 200) (aj) the heavy chain variable region and / or the light chain variable region of antibody Fab9 (SEQ ID NO: 206 and / or SEQ ID NO: 204) (ak) the heavy chain variable region and / or the light chain variable region of antibody Fab10 (SEQ ID NO: 210 and / or SEQ ID NO: 208) (al) the heavy chain variable region and / or the light chain variable region of antibody Fab11 (SEQ ID NO: 214 and / or SEQ ID NO: 212) and / or (am) the heavy chain variable region and / or the light chain variable region of antibody mAb2 (SEQ ID NO: 387 and / or SEQ ID NO: 385). In a preferred embodiment, B1 may comprise the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NO: 430 and / or SEQ ID NO: 431) and B2 may comprise the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NO: 433 and / or SEQ ID NO: 432). The B1 domain may comprise the light chain variable region and / or the heavy chain variable region of any B1 domain described above, and the B2 domain may comprise the light chain variable region and / or the heavy chain variable region of any B2 domain described above, or variants of said light chain variable regions and / or said heavy chain variable regions having at least 90% sequence identity thereto. Typically, the bispecific polypeptides will comprise constant region sequences, in addition to the above-defined variable region sequences. The bispecific polypeptides may be in any suitable format. For example, bispecific polypeptides may be in the RUBY™ format or optimised RUBY™ format (as described above, and shown in Figure 23), or in the Morrison format. An exemplary heavy chain constant region amino acid sequence which may be combined with any VH region sequence disclosed herein (to form a complete heavy chain) is the following IgG1 heavy chain constant region sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK (SEQ ID NO: 349) Likewise, an exemplary light chain constant region amino acid sequence which may be combined with any VL region sequence disclosed herein (to form a complete light chain) is the Kappa chain constant region sequence reproduced here: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 350) Other light chain constant region sequences are known in the art and could also be combined with any VL region disclosed herein. In one embodiment, the polypeptide may comprise the following constant region amino acid sequences: (a) Reference sequence CH1 (SEQ ID NO: 354): ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC (wherein the bold and underlined section is part of the hinge region, but is present in the Fab fragment) and / or (b) Reference sequence CKappa (SEQ ID NO: 355): RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC and / or Reference sequence CLambda (SEQ ID NO: 356) GQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS and / or Reference sequence CLambda (SEQ ID NO: 357) GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNN KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS and / or Reference sequence CLambda (SEQ ID NO: 358) GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNN KYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS As described above, these reference sequences may comprise one or more mutations to prevent the formation of aggregates and / or a Fab by-product. Such mutation positions (identified earlier in the description) may be given relative to any of the above constant region sequences. In one embodiment, the bispecific polypeptide is in the RUBY™ format or in the optimised RUBY™ format, comprising an immunoglobulin and a Fab fragment, wherein the Fab fragment is fused to the C-terminus of the heavy chain of the immunoglobulin via the light chain of the Fab fragment. Thus in one embodiment, binding domain B1 is an immunoglobulin, and binding domain B2 is a Fab fragment, and the Fab fragment is fused to the C-terminus of the heavy chain of the immunoglobulin via the light chain of the Fab fragment. In an alternative embodiment, binding domain B2 is an immunoglobulin, and binding domain B1 is a Fab fragment, and the Fab fragment is fused to the C-terminus of the heavy chain of the immunoglobulin via the light chain of the Fab fragment. Additionally, the bispecific polypeptide comprises one or more mutations selected from those described above for the RUBY™ format and / or the optimised RUBY™ format. In one embodiment, the bispecific polypeptide comprises a binding domain B1 and / or a binding domain 2 comprising the light chain CDRs and / or heavy chain CDRs, and / or the format, of an antibody selected from the list consisting of: Multi1; Multi2; Multi3; Multi4; Multi5; Multi6; Multi7; Multi8; Multi9; Multi10; Multi11; Multi12; Multi13; Multi14; Multi17; Multi18; Multi19; Multi20; Multi23; Multi24; Multi25; Multi26; Multi27; Multi28; Multi29; Multi30; Multi31; Multi32; Multi33; Multi34; Multi35; Multi37; Multi38; Multi39; Multi40; Multi41; Multi42; Multi44; Multi46; Multi47; Multi48; Multi49; AC_05333; AC_05334; AC_05336; AC_05337; AC_05338; AC_05339; AC_05341; ffAC_05337; ffAC_05339; and / or AC_05355, preferably Multi34; Multi42; Multi46 and / or ffAC_05337. In one embodiment, the bispecific polypeptide comprises a binding domain B1 and / or a binding domain 2 comprising the light chain variable region and / or heavy chain variable region, and / or the format, of an antibody selected from the list consisting of: Multi1; Multi2; Multi3; Multi4; Multi5; Multi6; Multi7; Multi8; Multi9; Multi10; Multi11; Multi12; Multi13; Multi14; Multi17; Multi18; Multi19; Multi20; Multi23; Multi24; Multi25; Multi26; Multi27; Multi28; Multi29; Multi30; Multi31; Multi32; Multi33; Multi34; Multi35; Multi37; Multi38; Multi39; Multi40; Multi41; Multi42; Multi44; Multi46; Multi47; Multi48; Multi49; AC_05333; AC_05334; AC_05336; AC_05337; AC_05338; AC_05339; AC_05341; ffAC_05337; ffAC_05339; and / or AC_05355, preferably Multi34; Multi42; Multi46 and / or ffAC_05337. In one embodiment, the bispecific polypeptide comprises a binding domain B1 and / or a binding domain 2 comprising the light chain and / or heavy chain, and / or the format, of an antibody selected from the list consisting of: Multi1; Multi2; Multi3; Multi4; Multi5; Multi6; Multi7; Multi8; Multi9; Multi10; Multi11; Multi12; Multi13; Multi14; Multi17; Multi18; Multi19; Multi20; Multi23; Multi24; Multi25; Multi26; Multi27; Multi28; Multi29; Multi30; Multi31; Multi32; Multi33; Multi34; Multi35; Multi37; Multi38; Multi39; Multi40; Multi41; Multi42; Multi44; Multi46; Multi47; Multi48; Multi49; AC_05333; AC_05334; AC_05336; AC_05337; AC_05338; AC_05339; AC_05341; ffAC_05337; ffAC_05339; and / or AC_05355, preferably Multi34; Multi42; Multi46 and / or ffAC_05337. In one embodiment, the bispecific polypeptide comprises a Chain H1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 359; SEQ ID NO: 362; SEQ ID NO: 365; and / or SEQ ID NO: 367. In one embodiment, the bispecific polypeptide comprises a Chain L1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 360; SEQ ID NO: 363; SEQ ID NO: 372; and / or SEQ ID NO: 368. In one embodiment, the bispecific polypeptide comprises a Chain H2 comprising a sequence selected from the listing consisting of: SEQ ID NO: 361; SEQ ID NO: 364; SEQ ID NO: 366; and / or SEQ ID NO: 369. In one embodiment, the bispecific polypeptide: x comprises a Chain H1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 359; SEQ ID NO: 362; SEQ ID NO: 365; and / or SEQ ID NO: 367; and / or x comprises a Chain L1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 360; SEQ ID NO: 363; SEQ ID NO: 372; and / or SEQ ID NO: 368; and / or x comprises a Chain H2 comprising a sequence selected from the listing consisting of: SEQ ID NO: 361; SEQ ID NO: 364; SEQ ID NO: 366; and / or SEQ ID NO: 369. In one embodiment, the bispecific polypeptide: x comprises two Chain H1 each comprising a sequence selected from the listing consisting of: SEQ ID NO: 359; SEQ ID NO: 362; SEQ ID NO: 365; and / or SEQ ID NO: 367; and / or x comprises two Chain L1 each comprising a sequence selected from the listing consisting of: SEQ ID NO: 360; SEQ ID NO: 363; SEQ ID NO: 372; and / or SEQ ID NO: 368; and / or x comprises two Chain H2 each comprising a sequence selected from the listing consisting of: SEQ ID NO: 361; SEQ ID NO: 364; SEQ ID NO: 366; and / or SEQ ID NO: 369. In one embodiment the bispecific polypeptide may comprise one or more variants of the above-defined Chain H1, Chain L1, and / or Chain H2 having at least 90% sequence identity thereto or 95% sequence identity thereto or 99% sequence identity thereto. In one embodiment, the bispecific polypeptide: x comprises a Chain H1 comprising SEQ ID NO: 359; and / or x comprises a Chain L1 comprising SEQ ID NO: 360; and / or x comprises a Chain H2 comprising SEQ ID NO: 361. In one embodiment, the bispecific polypeptide: x comprises a Chain H1 comprising SEQ ID NO: 362; and / or x comprises a Chain L1 comprising SEQ ID NO: 363; and / or x comprises a Chain H2 comprising SEQ ID NO: 364;. In one embodiment, the bispecific polypeptide: x comprises a Chain H1 comprising SEQ ID NO: 365; and / or x comprises a Chain L1 comprising SEQ ID NO: 372; and / or x comprises a Chain H2 comprising SEQ ID NO: 366. In one embodiment, the bispecific polypeptide: x comprises a Chain H1 comprising SEQ ID NO: 367; and / or x comprises a Chain L1 comprising SEQ ID NO: 368; and / or x comprises a Chain H2 comprising SEQ ID NO: 369. In one embodiment, the bispecific polypeptide: x comprises two Chain H1 comprising SEQ ID NO: 359; and / or x comprises two Chain L1 comprising SEQ ID NO: 360; and / or x comprises two Chain H2 comprising SEQ ID NO: 361. In one embodiment, the bispecific polypeptide: x comprises two Chain H1 comprising SEQ ID NO: 362; and / or x comprises two Chain L1 comprising SEQ ID NO: 363; and / or x comprises two Chain H2 comprising SEQ ID NO: 364;. In one embodiment, the bispecific polypeptide: x comprises two Chain H1 comprising SEQ ID NO: 365; and / or x comprises two Chain L1 comprising SEQ ID NO: 372; and / or x comprises two Chain H2 comprising SEQ ID NO: 366. In one embodiment, the bispecific polypeptide: x comprises two Chain H1 comprising SEQ ID NO: 367; and / or x comprises two Chain L1 comprising SEQ ID NO: 368; and / or x comprises two Chain H2 comprising SEQ ID NO: 369. In one embodiment, the bispecific polypeptide is an antibody selected from the list consisting of: Multi1; Multi2; Multi3; Multi4; Multi5; Multi6; Multi7; Multi8; Multi9; Multi10; Multi11; Multi12; Multi13; Multi14; Multi17; Multi18; Multi19; Multi20; Multi23; Multi24; Multi25; Multi26; Multi27; Multi28; Multi29; Multi30; Multi31; Multi32; Multi33; Multi34; Multi35; Multi37; Multi38; Multi39; Multi40; Multi41; Multi42; Multi44; Multi46; Multi47; Multi48; Multi49; AC_05333; AC_05334; AC_05336; AC_05337; AC_05338; AC_05339; AC_05341; ffAC_05337; ffAC_05339; and / or AC_05355, preferably Multi34; Multi42; Multi46 and / or ffAC_05337. In one embodiment the bispecific polypeptide may comprise one or more variants of the above-defined Multi1; Multi2; Multi3; Multi4; Multi5; Multi6; Multi7; Multi8; Multi9; Multi10; Multi11; Multi12; Multi13; Multi14; Multi17; Multi18; Multi19; Multi20; Multi23; Multi24; Multi25; Multi26; Multi27; Multi28; Multi29; Multi30; Multi31; Multi32; Multi33; Multi34; Multi35; Multi37; Multi38; Multi39; Multi40; Multi41; Multi42; Multi44; Multi46; Multi47; Multi48; Multi49; AC_05333; AC_05334; AC_05336; AC_05337; AC_05338; AC_05339; AC_05341; ffAC_05337; ffAC_05339; and / or AC_05355 having at least 90% sequence identity thereto or 95% sequence identity thereto or 99% sequence identity thereto. Exemplary full heavy and light chain sequences Binding domain B1: 1132 / 1133 Heavy chain, including RUBY mutations (VH: Q44R, CH1: H168A, F170G, CH2: L234A, L235A) (SEQ ID NO: 371): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRRAPGKGLEWVSGIGSYGGGTYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYVNFGMDYWGQGTLVTVSSASTKGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVATGPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1132 / 1133 Light chain, including RUBY mutations (VL: Q44E, CKappa: L135Y, S176W) (SEQ ID NO: 372): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQEKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQYGRNPPTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCYLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLWSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC 1132 / 1133 Heavy chain (SEQ ID NO: 378): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGIGSYGGGTYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYVNFGMDYWGQGTLVTVSSASTKGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K 1132 / 1133 Light chain (SEQ ID NO: 379): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQYGRNPPTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC G12 Heavy chain (SEQ ID NO: 380): EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWLSYISGGSSYIFYADS VRGRFTISRDNSENALYLQMNSLRAEDTAVYYCARILRGGSGMDLWGQGTLVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK G12 Light chain (SEQ ID NO: 381): QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYNVYWYQQLPGTAPKLLIYGNINRPSGVPDRF SGSKSGTSASLAISGLRSEDEADYYCAAWDKSISGLVFGGGTKLTVLGQPKAAPSVTLFPPSSE ELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKS HRSYSCQVTHEGSTVEKTVAPTECS G12_mut Heavy chain (SEQ ID NO: 382): EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWLSYISGGSSYIFYADS VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARILRGGSGMDLWGQGTLVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK G12_mut Light chain (SEQ ID NO: 383): QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYNVYWYQQLPGTAPKLLIYGNINRPSGVPDRF SGSKSGTSASLAISGLRSEDEADYYCAAWDKSISGLVFGGGTKLTVLGQPKAAPSVTLFPPSSE ELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKS HRSYSCQVTHEGSTVEKTVAPTECS Binding domain B2: AC_05059, light chain (SEQ ID NO: 388): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05059, heavy chain (SEQ ID NO: 389):EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYST SYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPPHLDYWGQGTLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK AC_05060, light chain (SEQ ID NO: 390): DIQMTQSPSSLSASVGDRVTITCRASQSIRDYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQGTFPFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTAS VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC EVTHQGLSSPVTKSFNRGEC AC_05060, heavy chain (SEQ ID NO: 391): EVQLLESGGGLVQPGGSLRLSCAASGFTFGSYYMSWVRQAPGKGLEWVSGISGYGYYTGYADS VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHGYGVIDYWGQGTLVTVSSASTKGPSVFP LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK AC_05061, light chain (SEQ ID NO: 392): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQGAYVPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05061, heavy chain (SEQ ID NO: 393): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGYTHFDYWGQGTLVTVSSASTKGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K AC_05062, light chain (SEQ ID NO: 394): DIQMTQSPSSLSASVGDRVTITCRASQAISGYLNWYQQKPGKAPKLLIYSASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05062, heavy chain (SEQ ID NO: 395): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYRWHGSVFDYWGQGTLVTVSSASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05064, light chain (SEQ ID NO: 396): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQYPWYFPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY ACEVTHQGLSSPVTKSFNRGEC AC_05064, heavy chain (SEQ ID NO: 397): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGYSVLDYWGQGTLVTVSSASTKGPSVF PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K AC_05079, light chain (SEQ ID NO: 398): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05079, heavy chain (SEQ ID NO: 399): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPPPLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05081, light chain (SEQ ID NO: 400): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05081, heavy chain (SEQ ID NO: 401): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFQPHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05088, light chain (SEQ ID NO: 402): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05088, heavy chain (SEQ ID NO: 403): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVLFPPHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05089, light chain (SEQ ID NO: 404): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05089, heavy chain (SEQ ID NO: 405): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPHHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05090, light chain (SEQ ID NO: 406): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05090, heavy chain (SEQ ID NO: 407): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPLHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05091, light chain (SEQ ID NO: 408): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05091, heavy chain (SEQ ID NO: 409): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPPHFDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05093, light chain (SEQ ID NO: 410): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05093, heavy chain (SEQ ID NO: 411): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPPHVDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05094, light chain (SEQ ID NO: 412): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05094, heavy chain (SEQ ID NO: 413): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFPPHWDYWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK AC_05096, light chain (SEQ ID NO: 414): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05096, heavy chain (SEQ ID NO: 415): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFRPHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK AC_05097, light chain (SEQ ID NO: 416): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQAGNPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTA SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC AC_05097, heavy chain (SEQ ID NO: 417): EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIGSGSYSTSYAD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYPSVPFSPHLDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK Fab1, light chain (SEQ ID NO: 418): DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQSSHGPLLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY ACEVTHQGLSSPVTKSFNRGEC Fab1, heavy chain (SEQ ID NO: 419): QVQLVQSGAEVKKPGSSVKVSCKASGGTFGYYAIHWVRQAPGQGLEWMGGIGSIFGTANYAQ KFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAWSSDHMDYWGQGTLVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK Fab3, light chain (SEQ ID NO: 420): EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSG SGSGTDFTLTISRLEPEDFAVYYCQQYWYPLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTAS VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC EVTHQGLSSPVTKSFNRGEC Fab3, heavy chain (SEQ ID NO: 421): QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSSSIHWVRQAPGQGLEWMGHIYPSFGTANYAQ KFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARHSGSRFFSPMDYWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK As discussed above, methods for the production of bispecific polypeptides are well known in the art. Conveniently, the bispecific polypeptide is or comprises a recombinant polypeptide. Suitable methods for the production of such recombinant polypeptides are well known in the art, such as expression in prokaryotic or eukaryotic hosts cells (for example, see Green & Sambrook, 2012, Molecular Cloning, A Laboratory Manual, Fourth Edition, Cold Spring Harbor, New York, the relevant disclosures in which document are hereby incorporated by reference). Polypeptides as described can also be produced using a commercially available in vitro translation system, such as rabbit reticulocyte lysate or wheatgerm lysate (available from Promega). Preferably, the translation system is rabbit reticulocyte lysate. Conveniently, the translation system may be coupled to a transcription system, such as the TNT transcription-translation system (Promega). This system has the advantage of producing suitable mRNA transcript from an encoding DNA polynucleotide in the same reaction as the translation. It will be appreciated by persons skilled in the art that bispecific polypeptides may alternatively be synthesised artificially, for example using well known liquid-phase or solid phase synthesis techniques (such as t-Boc or Fmoc solid-phase peptide synthesis). PD-1 inhibitors The combination therapies, pharmaceutical compositions, use and methods of the invention comprise a PD-1 inhibitor. The PD-1 inhibitor may be effective in the treatment of cancer and / or may specifically bind to PD-1 or PD-L1. It will be appreciated that the therapeutic benefit of the PD-1 inhibitor may be mediated by attenuating the function of the inhibitory immune checkpoint molecule PD-1. Thus, in an embodiment of the invention, the PD-1 inhibitor is an immunotherapeutic agent with efficacy in the treatment of cancer. The term "immunotherapeutic agent" is intended to include any molecule, peptide, antibody or other agent which can stimulate a host immune system to generate an immune response to a tumour or cancer in the subject. Various immunotherapeutic agents are useful in the compositions and methods described herein. In one embodiment, the immunotherapeutic agent is an antibody or antigen-binding fragment thereof, such as an anti-PD-1 antibody that is capable of specifically binding PD-1 or an anti-PD-L1 antibody which is capable of specifically binding PD-L1. The term "immune response" includes T cell mediated and / or B cell mediated immune responses. Exemplary immune responses include T cell responses, e.g., cytokine production and cellular cytotoxicity. In addition, the term immune response includes immune responses that are indirectly effected by T cell activation, e.g., antibody production (humoral responses) and activation of cytokine responsive cells, e.g., macrophages. Immune checkpoint molecules include a group of proteins on the cell surface of immune cells, such as CD4+ and / or CD8+ T cells, dendritic cells, NK cells and macrophages but also on certain tumor cells, that modulate immune responses. It will be appreciated by persons skilled in the art that PD-1 is an inhibitory immune check point molecule. Blocking or neutralisation of inhibitory immune checkpoint molecules, such as PD-1, can block or otherwise neutralise inhibitory signalling to thereby upregulate an immune response in order to more efficaciously treat cancer. Exemplary agents useful for blocking inhibitory immune checkpoint include antibodies, small molecules, peptides, peptidomimctics, natural ligands, and derivatives of natural ligands, that can either bind and / or inactivate or inhibit inhibitory immune checkpoint proteins, or fragments thereof; as well as RNA interference, antisense, nucleic acid aptamers, etc. that can downregulate the expression and / or activity of inhibitory immune checkpoint nucleic acids, or fragments thereof. Exemplary agents for upregulating an immune response include antibodies against one or more inhibitory immune checkpoint proteins that blocks the interaction between the proteins and its natural receptor(s); a non- activating form of one or more immune checkpoint inhibitor proteins {e.g., a dominant negative polypeptide): small molecules or peptides that block the interaction between one or more inhibitory immune checkpoint proteins and its natural receptor(s); fusion proteins (e.g. the extracellular portion of an immune checkpoint inhibition protein fused to the Fc portion of an antibody or immunoglobulin) that bind to its natural receptor(s); nucleic acid molecules that block inhibitory immune checkpoint nucleic acid transcription or translation; and the like. Such agents can directly block the interaction between the one or more inhibitory immune checkpoint and its natural receptor(s) (e.g., antibodies) to prevent inhibitory signalling and upregulate an immune response. Alternatively, agents can indirectly block the interaction between one or more inhibitory immune checkpoint proteins and its natural receptor(s) to prevent inhibitory signalling and upregulate an immune response. For example, a soluble version of an immune checkpoint protein ligand such as a stabilized extracellular domain can binding to its receptor to indirectly reduce the effective concentration of the receptor to bind to an appropriate ligand. In one embodiment, anti-PD-1 antibodies and / or anti-PD-L1 antibodies either alone or in combination, are used to inhibit immune checkpoint inhibitors. Thus, in one embodiment, the PD-1 inhibitor that binds to and inhibits the function of an inhibitory immune checkpoint molecule. By “PD-1 inhibitor” (or “PD-1 pathway inhibitor”) we include an entity which is capable of inhibiting the PD-1 pathway. PD-1 serves as a negative regulator of T cell activation when engaged with its ligands PD-L1 or PD-L2. PD-L1 in particular is expressed by many solid tumors, including melanoma. These tumours may therefore down regulate immune mediated anti-tumor effects through activation of the inhibitory PD-1 receptors on T cells. By blocking the interaction between PD-1 and PD-L1, a check point of the immune response may be removed, leading to augmented anti-tumour T cell responses. This interaction may be blocked by an antibody specific for PD-1 or PD-L1 or any other suitable agent. Such antibodies and agents may be generally referred to as PD-1 inhibitors. Accordingly, PD-1 inhibitors block the interaction of PD-1 (programmed cell death protein 1) with its ligand PD-L1 (programmed death-ligand 1). Such PD-1 inhibitors can therefore act on either, or both, PD-L1 and PD-1. Thus, the term PD-1 inhibitors includes both PD-1 and PD-L1 inhibitors. PD-1 inhibitors block the activity of PD-1 and PD-L1 immune checkpoint proteins. In some embodiments, the PD-1 inhibitor is an anti-PD-1 antibody or antigen binding fragment thereof. In some embodiments, the PD-1 inhibitor is an anti-PD-L1 antibody or antigen binding fragment thereof. By “PD-1”, we specifically include the human PD-1 protein, for example as described in GenBank Accession No. NP_005009.2 (the sequence of which is set out in SEQ ID NO: 470 below). PD-1 is also know in the scientific literature as PD1, CD279, PDCD1 and SLEB2. MQIPQAPWPV VWAVLQLGWR PGWFLDSPDR PWNPPTFSPA LLVVTEGDNA TFTCSFSNTS ESFVLNWYRM SPSNQTDKLA AFPEDRSQPG QDCRFRVTQL PNGRDFHMSV VRARRNDSGT YLCGAISLAP KAQIKESLRA ELRVTERRAE VPTAHPSPSP RPAGQFQTLV VGVVGGLLGS LVLLVWVLAV ICSRAARGTI GARRTGQPLK EDPSAVPVFS VDYGELDFQW REKTPEPPVP CVPEQTEYAT IVFPSGMGTS SPARRGSADG PRSAQPLRPE DGHCSWPL [SEQ ID NO: 470] By “PD-L1” we specifically include the human PD-L1 protein, for example as described in GenBank Accession No. AAI13735.1 (the sequence of which is set out in SEQ ID NO: 471 below). PD-L1 is also know in the scientific literature as CD274, B7-H1, B7-H, PDCD1L1 and PDCD1LG1 MRIFAVFIFM TYWHLLNAFT VTVPKDLYVV EYGSNMTIEC KFPVEKQLDL AALIVYWEME DKNIIQFVHG EEDLKVQHSS YRQRARLLKD QLSLGNAALQ ITDVKLQDAG VYRCMISYGG ADYKRITVKV NAPYNKINQR ILVVDPVTSE HELTCQAEGY PKAEVIWTSS DHQVLSGKTT TTNSKREEKL FNVTSTLRIN TTTNEIFYCT FRRLDPEENH TAELVIPELP LAHPPNERTH LVILGAILLC LGVALTFIFR LRKGRMMDVK KCGIQDTNSK KQSDTHLEET [SEQ ID NO: 471] Thus, the combination therapy or pharmaceutical composition of the invention comprises a PD-1 inhibitor that specifically binds to PD-1 or PD-L1 i.e. has specificity for PD-1 or PD-L1. By “specificity” we mean that the inhibitor is capable of binding to PD-1 or PD-L1 in vivo, i.e. under the physiological conditions in which PD-1 or PD-L1 exists within the human body. Preferably, the PD-1 inhibitor does not bind to any other protein (other than PD-1 or PD-L1) in vivo. Such binding specificity may be determined by methods well known in the art, such as ELISA, immunohistochemistry, immunoprecipitation, Western blots and flow cytometry using transfected cells expressing PD-1 or PD-L1. The PD-1 inhibitor that specifically binds to PD-1 or PD-L1 preferably binds to human PD-1 or PD-L1 with a Kd value which is less than 10x10-9M or less than 7x10-9M, more preferably less than 4, or 2x10-9M, most preferably less than 1.2x10-9M. Advantageously, the PD-1 inhibitor is capable of binding selectively to PD-1 or PD-L1, i.e. it bind at least 10-fold more strongly to PD-1 or PD-L1 than to any other proteins. The PD-1 inhibitor preferably specifically binds to PD-1 or PD-L1, i.e. it binds to PD-1 or PD-L1 but does not bind, or binds at a lower affinity (e.g. a 10-fold lower affinity), to other molecules (such as OX40 and / or CD40) – it therefore binds to PD-1 or PD-L1 with greater binding affinity than that at which it binds another molecule. Therefore, typically, the Kd for the antibody with respect to human PD-1 or PD-L1 will be 2-fold, preferably 5-fold, more preferably 10-fold less than Kd with respect to the other, non- target molecule, such as murine PD-1 or PD-L1, other immune checkpoint molecules, or any other unrelated material or accompanying material in the environment. More preferably, the Kd will be 50-fold less, even more preferably 100-fold less, and yet more preferably 200-fold less. Methods for measuring the overall affinity (KD) and on-rate (ka) and off-rate (kd) of an interaction (such as an interaction between an antibody and a ligand) are well known in the art. Exemplary in vitro methods are described in the accompanying Examples. It is also conceivable to use flow cytometry based methods (Sklar et al., Annu Rev Biophys Biomol Struct, (31), 97-119, 2002). The terms PD-1 and PD-L1 as used herein typically refers to human PD-1 and PD-L1. The inhibitor may have some binding affinity for PD-1 or PD-L1 from other mammals, such as PD-1 or PD-L1 from a non-human primate, for example Macaca fascicularis (cynomolgus monkey). The antibody preferably does not bind to murine PD-1 or PD- L1 and / or does not bind to other immune checkpoint molecules. In an embodiment, the PD-1 inhibitor thereof that specifically binds to PD-1 or PD-L1 may have affinity for PD-1 or PD-L1 in its native state, for example for PD-1 or PD-L1 localised on the surface of a cell. In an embodiment, the PD-1 inhibitor blocks the PD-1 PD-L1 interaction. For example, the PD-1 inhibitor may bind to PD-1 or PD-L1 in a manner that inhibits the ability of PD-L1 to bind to PD-1, thereby blocking the PD- 1 / PD-L1 interaction. By “localised on the surface of a cell” it is meant that PD-1 or PD-L1 is associated with the cell such that one or more region of PD-1 is present on the outer face of the cell surface. For example, PD-1 may be inserted into the cell plasma membrane (i.e. orientated as a transmembrane protein) with one or more regions presented on the extracellular surface. This may occur in the course of expression of PD-1 by the cell. Thus, in one embodiment, “localised on the surface of a cell” may mean “expressed on the surface of a cell.” Alternatively, PD-1 may be outside the cell with covalent and / or ionic interactions localising it to a specific region or regions of the cell surface. In an embodiment, the PD-1 inhibitors described here are capable of inducing antitumour immunity, via immune checkpoint blockade. The PD-1 inhibitor binds to PD-1 or PD-L1 in a manner that inhibits PD-L1 to bind to PD-1, i.e. blocks the PD-1 / PD- L1 interaction. The PD-1 inhibitor may be capable of enhancing T cell responses, for example it may be capable of enhancing or restoring T cell effector function. In one embodiment the PD-1 inhibitor may promote infiltration of tumour reactive CD8+ T cells into established tumours. Thus, PD-1 inhibitor may modulate the activity of a cell expressing PD-1 or PD-L1, wherein said modulation is an increase or decrease in the activity of said cell. The cell is typically a T cell. The inhibitor may increase the activity of a CD4+ or CD8+ effector cell, or may decrease the activity of, or deplete, a regulatory T cell (T reg). In either case, the net effect of the antibody will be an increase in the activity of effector T cells, particularly CD4+, CD8+ or NK effector T cells. Methods for determining a change in the activity of effector T cells are well known and are as described earlier. The PD-1 inhibitor preferably causes an increase in activity in a T cell in vitro, preferably a CD8+ T cell, optionally wherein said increase in activity is an increase in proliferation, IFN-DŽ production and / or IL-2 production by the T cell. The increase is preferably at least 2-fold, more preferably at least 10-fold and even more preferably at least 25-fold higher than the change in activity caused by an isotype control antibody measured in the same assay. In one embodiment, the PD-1 inhibitors are capable of improving efficacy of another immunotherapy. In one embodiment, the PD-1 inhibitor blocks the programmed death-1 (PD-1) receptor binding to its ligand PD-L1, expressed on the surface of cells within a tumor (Ribas and Wolchok 2018). PD-1 is an immune checkpoint, with its inhibitory function mediated by the tyrosine phosphatase SHP-2 that de-phosphorylates signaling molecules downstream of the T cell receptor (TCR) signaling molecules. In a preferred embodiment, the PD-1 inhibitor reactivates PD-1 expressing T cells, preferably by blocking the inhibitory signaling mediated by the tyrosine phosphatase SHP-2 (that de- phosphorylates signaling molecules downstream of the T cell receptor (TCR) signaling molecules. The PD-1 inhibitor may be an anti-PD-1 antibody, or antigen-binding fragment thereof capable of inhibiting PD-1 function (for example, Pembrolizumab (also known as Lambrolizumab), Nivolumab, Pidilizumab, Cemiplimab, AMP-224, PDR-001,MEDI- 0680 (also known as AMP-514), JTX-4014 (Pimivalimab), Spartalizumab, Camrelizumab, Sintilimab, Tislelizumab, Toripalimab, Dostarlimab, INCMGA00012 (Retifanlimab) and Acrixolimab (YBL 006). Alternatively, the PD-1 inhibitor may comprise or consist of an anti-PD-L1 antibody, or antigen-binding fragment thereof capable of inhibiting PD-1 function (for example, Atezolizumab (Tecentriq™, MPDL3280A), Durvalumab (MEDI-4736), Avelumab, MDX- 1105, KN035 (Envafolimab) and CK-301 (Cosibelimab)). Alternatively the PD-1 inhibitor may be a small molecule or peptide based inhibitor of PD-1 or PD-L1. For example the PD-1 inhibitor may be a small molecule inhibitor of PD-L1 such as CA-170. Alternatively, the PD-1 inhibitor may be a peptide inhibitor of PD-L1 such as AUNP12 or BMS-986189. The PD-1 inhibitor is formulated for parenteral delivery. By parenteral delivery we include any non-oral means of delivery. In some preferred embodiments, the PD-1 inhibitor is formulated for intraveneous, subcutaneous or intratumoral delivery. In some embodiments, the PD-1 inhibitor is formulated for intraveneous delivery. In one embodiment, the PD-1 inhibitor binds to an epitope that blocks the PD-1 PD-L1 interaction. By “Pembrolizumab” we mean an intact IgG antibody comprising heavy and light chains having the amino acid sequences of SEQ ID NOS: 440 and 441, respectively. Heavy chain sequence of Pembrolizumab (SEQ ID NO: 440): QVQLVQSGVE VKKPGASVKV SCKASGYTFT NYYMYWVRQA PGQGLEWMGG INPSNGGTNF NEKFKNRVTL TTDSSTTTAY MELKSLQFDD TAVYYCARRD YRFDMGFDYW GQGTTVTVSS ASTKGPSVFP LAPCSRSTSE STAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTKT YTCNVDHKPS NTKVDKRVES KYGPPCPPCP APEFLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSQED PEVQFNWYVD GVEVHNAKTK PREEQFNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKGLPS SIEKTISKAK GQPREPQVYT LPPSQEEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSRL TVDKSRWQEG NVFSCSVMHE ALHNHYTQKS LSLSLGK Light chain sequence of Pembrolizumab (SEQ ID NO: 441) EIVLTQSPAT LSLSPGERAT LSCRASKGVS TSGYSYLHWY QQKPGQAPRL LIYLASYLES GVPARFSGSG SGTDFTLTIS SLEPEDFAVY YCQHSRDLPL TFGGGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC By “Nivolumab” we mean an intact IgG antibody comprising heavy and light chains having the amino acid sequences of SEQ ID NOS: 442 and 443, respectively. Heavy chain sequence of Nivolumab (SEQ ID NO: 442): QVQLVESGGG VVQPGRSLRL DCKASGITFS NSGMHWVRQA PGKGLEWVAV IWYDGSKRYY ADSVKGRFTI SRDNSKNTLF LQMNSLRAED TAVYYCATND DYWGQGTLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TKTYTCNVDH KPSNTKVDKR VESKYGPPCP PCPAPEFLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS QEDPEVQFNW YVDGVEVHNA KTKPREEQFN STYRVVSVLT VLHQDWLNGK EYKCKVSNKG LPSSIEKTIS KAKGQPREPQ VYTLPPSQEE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SRLTVDKSRW QEGNVFSCSV MHEALHNHYT QKSLSLSLGK Light chain sequence of Nivolumab (SEQ ID NO: 443) EIVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQQ SSNWPRTFGQ GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of Pidilizumab (SEQ ID NO: 444) QVQLVQSGSE LKKPGASVKI SCKASGYTFT NYGMNWVRQA PGQGLQWMGW INTDSGESTY AEEFKGRFVF SLDTSVNTAY LQITSLTAED TGMYFCVRVG YDALDYWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK Light chain sequence of Pidilizumab (SEQ ID NO: 445) EIVLTQSPSS LSASVGDRVT ITCSARSSVS YMHWFQQKPG KAPKLWIYRT SNLASGVPSR FSGSGSGTSY CLTINSLQPE DFATYYCQQR SSFPLTFGGG TKLEIKRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC Heavy chain sequence of Cemiplimab (SEQ ID NO: 446) EVQLLESGGV LVQPGGSLRL SCAASGFTFS NFGMTWVRQA PGKGLEWVSG ISGGGRDTYF ADSVKGRFTI SRDNSKNTLY LQMNSLKGED TAVYYCVKWG NIYFDYWGQG TLVTVSSAST KGPSVFPLAP CSRSTSESTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTKTYTC NVDHKPSNTK VDKRVESKYG PPCPPCPAPE FLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSQEDPEV QFNWYVDGVE VHNAKTKPRE EQFNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKGLPSSIE KTISKAKGQP REPQVYTLPP SQEEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSRLTVD KSRWQEGNVF SCSVMHEALH NHYTQKSLSL SLGK Light chain sequence of Cemiplimab (SEQ ID NO: 447) DIQMTQSPSS LSASVGDSIT ITCRASLSIN TFLNWYQQKP GKAPNLLIYA ASSLHGGVPS RFSGSGSGTD FTLTIRTLQP EDFATYYCQQ SSNTPFTFGP GTVVDFRRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of Spartalizumab (SEQ ID NO: 448) EVQLVQSGAE VKKPGESLRI SCKGSGYTFT TYWMHWVRQA TGQGLEWMGN IYPGTGGSNF DEKFKNRVTI TADKSTSTAY MELSSLRSED TAVYYCTRWT TGTGAYWGQG TTVTVSSAST KGPSVFPLAP CSRSTSESTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTKTYTC NVDHKPSNTK VDKRVESKYG PPCPPCPAPE FLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSQEDPEV QFNWYVDGVE VHNAKTKPRE EQFNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKGLPSSIE KTISKAKGQP REPQVYTLPP SQEEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSRLTVD KSRWQEGNVF SCSVMHEALH NHYTQKSLSL SLG Light chain sequence of Spartalizumab (SEQ ID NO: 449) EIVLTQSPAT LSLSPGERAT LSCKSSQSLL DSGNQKNFLT WYQQKPGQAP RLLIYWASTR ESGVPSRFSG SGSGTDFTFT ISSLEAEDAA TYYCQNDYSY PYTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC Heavy chain sequence of Camrelizumab (SEQ ID NO: 450) EVQLVESGGG LVQPGGSLRL SCAASGFTFS SYMMSWVRQA PGKGLEWVAT ISGGGANTYY PDSVKGRFTIS RDNAKNSLYL QMNSLRAEDT AVYYCARQLY YFDYWGQGTT VTVSSASTKG PSVFPLAPCS RSTSESTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTKTYTCNV DHKPSNTKVD KRVESKYGPP CPPCPAPEFL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ FNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KGLPSSIEKT ISKAKGQPRE PQVYTLPPSQ EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF LYSRLTVDKS RWQEGNVFSC SVMHEALHNH YTQKSLSLSL GK Light chain sequence of Camrelizumab (SEQ ID NO: 451) DIQMTQSPSS LSASVGDRVT ITCLASQTIG TWLTWYQQKP GKAPKLLIYT ATSLADGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ VYSIPWTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of Tislelizumab (SEQ ID NO: 452) QVQLQESGPG LVKPSETLSL TCTVSGFSLT SYGVHWIRQP PGKGLEWIGV IYADGSTNYN PSLKSRVTIS KDTSKNQVSL KLSSVTAADT AVYYCARAYG NYWYIDVWGQ GTTVTVSSAS TKGPSVFPLA PCSRSTSEST AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTKTYT CNVDHKPSNT KVDKRVESKY GPPCPPCPAP PVAGGPSVFL FPPKPKDTLM ISRTPEVTCV VVAVSQEDPE VQFNWYVDGV EVHNAKTKPR EEQFNSTYRV VSVLTVVHQD WLNGKEYKCK VSNKGLPSSI EKTISKAKGQ PREPQVYTLP PSQEEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSKLTV DKSRWQEGNV FSCSVMHEAL HNHYTQKSLS LSLGK Light chain sequence of Tislelizumab (SEQ ID NO: 453) DIVMTQSPDS LAVSLGERAT INCKSSESVS NDVAWYQQKP GQPPKLLINY AFHRFTGVPD RFSGSGYGTD FTLTISSLQA EDVAVYYCHQ AYSSPYTFGQ GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of Toripalimab (SEQ ID NO: 454) QGQLVQSGAE VKKPGASVKV SCKASGYTFT DYEMHWVRQA PIHGLEWIGV IESETGGTAY NQKFKGRVTI TADKSTSTAY MELSSLRSED TAVYYCAREG ITTVATTYYW YFDVWGQGTT VTVSSASTKG PSVFPLAPCS RSTSESTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTKTYTCNV DHKPSNTKVD KRVESKYGPP CPPCPAPEFL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ FNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KGLPSSIEKT ISKAKGQPRE PQVYTLPPSQ EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF LYSRLTVDKS RWQEGNVFSC SVMHEALHNH YTQKSLSLSL GK Light chain sequence of Toripalimab (SEQ ID NO: 455) DVVMTQSPLS LPVTLGQPAS ISCRSSQSIV HSNGNTYLEW YLQKPGQSPQ LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDVGV YYCFQGSHVP LTFGQGTKLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK VQWKVDNALQ SGNSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE VTHQGLSSPV TKSFNRGEC Heavy chain sequence of Dostarlimab (SEQ ID NO: 456) EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYDMSWVRQA PGKGLEWVST ISGGGSYTYY QDSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCASPY YAMDYWGQGT TVTVSSASTK GPSVFPLAPC SRSTSESTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTKTYTCN VDHKPSNTKV DKRVESKYGP PCPPCPAPEF LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSQEDPEVQ FNWYVDGVEV HNAKTKPREE QFNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKGLPSSIEK TISKAKGQPR EPQVYTLPPS QEEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSRLTVDK SRWQEGNVFS CSVMHEALHN HYTQKSLSLS LGK Light chain sequence of Dostarlimab (SEQ ID NO: 457) DIQLTQSPSF LSAYVGDRVT ITCKASQDVG TAVAWYQQKP GKAPKLLIYW ASTLHTGVPS RFSGSGSGTE FTLTISSLQP EDFATYYCQH YSSYPWTFGQ GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of INCMGA00012 (SEQ ID NO: 458) QVQLVQSGAE VKKPGASVKV SCKASGYSFT SYWMNWVRQA PGQGLEWIGV IHPSDSETWL DQKFKDRVTI TVDKSTSTAY MELSSLRSED TAVYYCAREH YGTSPFAYWG QGTLVTVSSA STKGPSVFPL APCSRSTSES TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTKTY TCNVDHKPSN TKVDKRVESK YGPPCPPCPA PEFLGGPSVF LFPPKPKDTL MISRTPEVTC VVVDVSQEDP EVQFNWYVDG VEVHNAKTKP REEQFNSTYR VVSVLTVLHQ DWLNGKEYKC KVSNKGLPSS IEKTISKAKG QPREPQVYTL PPSQEEMTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN VFSCSVMHEA LHNHYTQKSL SLSLG Light chain sequence of INCMGA00012 (SEQ ID NO: 459) EIVLTQSPAT LSLSPGERAT LSCRASESVD NYGMSFMNWF QQKPGQPPKL LIHAASNQGS GVPSRFSGSG SGTDFTLTIS SLEPEDFAVY FCQQSKEVPY TFGGGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC By “Atezolizumab” we mean an intact IgG antibody comprising heavy and light chains having the amino acid sequences of SEQ ID NOS: 460 and 461, respectively. Heavy chain sequence of Atezolizumab (SEQ ID NO: 460) EVQLVESGGG LVQPGGSLRL SCAASGFTFS DSWIHWVRQA PGKGLEWVAW ISPYGGSTYY ADSVKGRFTI SADTSKNTAY LQMNSLRAED TAVYYCARRH WPGGFDYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYAST YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK Light chain sequence of Atezolizumab (SEQ ID NO: 461) DIQMTQSPSS LSASVGDRVT ITCRASQDVS TAVAWYQQKP GKAPKLLIYS ASFLYSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YLYHPATFGQ GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Heavy chain sequence of Durvalumab (SEQ ID NO: 462) EVQLVESGGG LVQPGGSLRL SCAASGFTFS RYWMSWVRQA PGKGLEWVAN IKQDGSEKYY VDSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCAREG GWFGELAFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPEFEG GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPASIEKTI SKAKGQPREP QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K Light chain sequence of Durvalumab (SEQ ID NO: 463) EIVLTQSPGT LSLSPGERAT LSCRASQRVS SSYLAWYQQK PGQAPRLLIY DASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSLPWTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC Heavy chain sequence of Avelumab (SEQ ID NO: 464) EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYIMMWVRQA PGKGLEWVSS IYPSGGITFY ADTVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARIK LGTVTTVDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK Light chain sequence of Avelumab (SEQ ID NO: 465) QSALTQPASV SGSPGQSITI SCTGTSSDVG GYNYVSWYQQ HPGKAPKLMI YDVSNRPSGV SNRFSGSKSG NTASLTISGL QAEDEADYYC SSYTSSSTRV FGTGTKVTVL GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADGSPVK AGVETTKPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS Heavy chain sequence of CK-301 (Cosibelimab) (SEQ ID NO: 466) EVQLVQSGAE VKKPGSSVKV SCKASGGTFS RSAISWVRQA PGQGLEWMGV IIPAFGEANY AQKFQGRVTI TADESTSTAY MELSSLRSED TAVYYCARGR QMFGAGIDFW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK Light chain sequence of CK-301 (Cosibelimab) (SEQ ID NO: 467) NFMLTQPHSV SESPGKTVTI SCTRSSGSID SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADYY CQSYDSNNRH VIFGGGTKLT VLGQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP VKAGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS Heavy chain sequence of JTX-4014 (SEQ ID NO: 468) QVQLVQSGAE VKKPGASVKV SCKASGYTFP SYYMHWVRQA PGQGLEWMGI INPEGGSTAY AQKFQGRVTM TRDTSTSTVY MELSSLRSED TAVYYCARGG TYYDYTYWGQ GTLVTVSSAS TKGPSVFPLA PCSRSTSEST AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTKTYT CNVDHKPSNT KVDKRVESKY GPPCPPCPAP EFLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSQEDPE VQFNWYVDGV EVHNAKTKPR EEQFNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKGLPSSI EKTISKAKGQ PREPQVYTLP PSQEEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSRLTV DKSRWQEGNV FSCSVMHEAL HNHYTQKSLS LSLGK Light chain sequence of JTX-4014 (SEQ ID NO: 469) DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYE ASSLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSFPPTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC Acrixolimab (formerly known as YBL 006) is an anti-PD1 monoclonal antibody having PubChem SID # 461454357 and CAS # 2506324-29-2. Such PD-1 inhibitors are also described in US8354509 B2 and US8779105 B2, and the PD-1 inhibitors (in particular anti-PD-1 antibodies) of US8354509 B2 and US8779105 B2 are incorporated herein by reference. For parenteral administration to human patients, the daily dosage level of the PD-1 inhibitor (e.g. anti-PD-1 and / or anti-PD-L1 antibody molecule) will usually be from 1 mg / kg bodyweight of the patient to 20 mg / kg, or in some cases even up to 100 mg / kg administered in single or divided doses. In some preferred embodiments, the dose is 10 mg / kg. Lower doses may be used in special circumstances, for example in combination with prolonged administration. The physician in any event will determine the actual dosage which will be most suitable for any individual patient and it will vary with the age, weight and response of the particular patient. The above dosages are exemplary of the average case. There can, of course, be individual instances where higher or lower dosage ranges are merited and such are within the scope of this invention. Typically, a combination therapy or pharmaceutical composition described herein will contain the PD-1 inhibitor (e.g. anti-PD-1 and / or anti-PD-L1 antibody molecule) at a concentration of between approximately 2 mg / ml and 150 mg / ml or between approximately 2 mg / ml and 200 mg / ml. In some embodiments, the pharmaceutical compositions will contain the anti-PD-1 and / or anti-PD-L1 antibody molecule at a concentration of from 10 mg / ml to 25 mg / ml. In some embodiments, the PD-1 inhibitor (e.g. anti-PD-1 and / or anti-PD-L1 antibody or antigen binding fragment thereof) is administered at a dose of from between 10 mg to 1500 mg. For example, the dose may be from 100 mg to 200 mg, or from 200 mg to 500 mg. In some embodiments, when the PD-1 inhibitor is the anti-PD-1 antibody pembrolizumab, the antibody is used at a dose of approximately 25 mg / ml. In some other embodiments, pembrolizumab is used at a dose of 200 mg (iv) every 3 weeks or at a dose of 400 mg (iv) every 6 weeks. In some embodiments, when the anti-PD-1 antibody is nivolumab, the antibody is used at a dose of approximately 10 mg / ml. In some embodiments, nivolumab is used at a dose of 240 mg (iv) every 2 weeks or at a dose of 480 mg (iv) every 4 weeks. In some embodiments, nivolumab may be used in combination with the anti-CTLA-4 antibody ipilimumab, in which case nivolumab is used at a dose of 1 mg / kg every 3 weeks for a maximum of 4 doses or 3 mg / kg every 2 or 3 weeks. In some embodiments, when the anti-PD-L1 antibody is atezolizumab, the antibody is used at a dose of approximately 60 mg / ml. In some other embodiments, atezolizumab is used at a dose of 840 mg (iv) every 2 weeks or at a dose of 1200 mg (iv) every 3 weeks or at a dose of 1680 mg (iv) every 4 weeks. In an embodiment the daily dosage level of the PD-1 inhibitor is: (a) from 1 mg / kg bodyweight of a subject to 100 mg / kg body weight of a subject; (b) From 1 mg / kg bodyweight of a subject to 20 mg / kg body weight of a subject; or (c) Is 1 mg / kg, 10 mg / kg, 20 mg / kg, 100 mg / kg bodyweight of a subject, preferably 10 mg / kg bodyweight. In an embodiment, the concentration of PD-1 inhibitor is between approximately 2 mg / ml and 150 mg / ml or between approximately 2 mg / ml and 200 mg / ml, preferably wherein the concentration of PD-1 inhibitor is from 10 mg / ml to 25 mg / ml. In an embodiment the dose of the PD-1 inhibitor is from between 10 mg to 1500 mg, optionally wherein the dose is from 100 mg to 200 mg, or from 200 mg to 500 mg. In an embodiment: (a) the PD-1 inhibitor is pembrolizumab used at a dose of approximately 25 mg / ml, 200mg (intravenous) every 3 weeks or 400 mg (intravenously) every 6 weeks; (b) the PD-1 inhibitor is nivolumab used at a dose of approximately 10 mg / ml, 250 mg (intravenous) every 2 weeks or 480 mg (intravenous) every 4 weeks; or (c) the PD-1 inhibitor is atezolizumab used a dose of approximately 60mg / ml. 840 mg (intravenous) every 2 weeks or 1200 mg (intravenous) every 4 weeks. In some embodiments, administration of the combination therapies described herein results in activation of exhausted T cells in a subject. By “exhausted T cells” we include a state in which T cells (CD4 or CD8) lose their ability to kill cells (e.g. cancer cells). Activation of exhausted T cells results in re-activation of these T cells. Advantageously, this leads to an enhancement in immune mediated killing of cancer cells. As shown herein in the Examples, the combination therapies described herein result in a synergistic effect on CD4 and CD8 T cell activity, as measured by IFN-DŽ levels. In some embodiments, the increased activation of exhausted T cells observed for the combination therapy is a synergistic effect compared to the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. By this we mean that the impact on T cell activation (as measured by IFN-DŽ levels, for example) for the combination therapy is greater than the additive effects of the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. In some embodiments, administration of the CD40xCEA bispecific antibody described herein results in upregulation of PD-1 and / or PD-L1 gene expression. In particular, the CD40xCEA bispecific antibody described herein has been shown to lead to upregulation of PD-L1 on the surface of tumour infiltrating immune cells. In some embodiments, administration of the CD40xCEA bispecific antibody described herein results in upregulation of PD-L1 on the surface of macrophages and / or dendritic cells. In some embodiments, administration of the combination therapies described herein results in improved reduction in tumour volume compared to administration of a control, a PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. In some embodiments, the improved reduction in tumour volume for the combination therapy is a synergistic effect compared to the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. By this we mean that the impact on tumour volume for the combination therapy is greater than the additive effects of the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. In some embodiments, administration of the combination therapies described herein results in increased survival compared to administration of a control, a PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. In some embodiments, the increased survival for the combination therapy is a synergistic effect compared to the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. By this we mean that the impact on survival for the combination therapy is greater than the additive effects of the PD-1 inhibitor alone, or a CD40xCEA bispecific antibody alone. In one embodiment, wherein the PD-1 inhibitor is an antibody or antigen binding fragment thereof, the antibodies or antigen-binding fragments that specifically bind to PD-1 or PD-L1 and are comprised in the combination therapy or pharmaceutical composition of the invention comprise an antibody Fc-region. It will be appreciated by a skilled person that the Fc portion may be from an IgG antibody, or from a different class of antibody (such as IgM, IgA, IgD or IgE). In one embodiment, the Fc region is from an IgG1, IgG2, IgG3 or IgG4 antibody. Advantageously, however, the Fc region is from an IgG4 antibody. The Fc region may be naturally-occurring (e.g. part of an endogenously produced antibody) or may be artificial (e.g. comprising one or more point mutations relative to a naturally-occurring Fc region). A variant of an Fc region typically binds to Fc receptors, such as FcDŽR and / or neonatal Fc receptor (FcRn) with altered affinity providing for improved function and / or half-life of the polypeptide. The biological function and / or the half-life may be either increased or a decreased relative to the half-life of a polypeptide comprising a native Fc region. Examples of such biological functions which may be modulated by the presence of a variant Fc region include antibody dependent cell cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and / or apoptosis. Thus, the Fc region may be naturally-occurring (e.g. part of an endogenously produced human antibody) or may be artificial (e.g. comprising one or more point mutations relative to a naturally-occurring human Fc region). As is well documented in the art, the Fc region of an antibody mediates its serum half- life and effector functions, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell phagocytosis (ADCP). Fc regions may be engineered as described above in relation to the bispecific antibodies of the combination therapy of the invention. Polynucleotides, vectors and cells A further aspect of the invention relates to a kit comprising a first isolated nucleic acid molecule encoding a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and: (i) a PD-1 inhibitor; and / or (ii) a second isolated nucleic acid molecule encoding an antibody or antigen binding fragment thereof that specifically binds to PD-1 or PD-L1 or a component polypeptide chain thereof. In an embodiment, the first isolated nucleic acid molecule encodes a bispecific polypeptide is as described earlier in relation to any other aspect of the invention, or is a component polypeptide chain thereof. For example, the nucleic acid molecule may comprise any of the nucleotide sequences provided in Tables A and B. Thus, the first polynucleotide may encode any polypeptide as described herein, or all or part of B1 or all or part of B2. The terms “nucleic acid molecule” and “polynucleotide” are used interchangeably herein and refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Non-limiting examples of polynucleotides include a gene, a gene fragment, messenger RNA (mRNA), cDNA, recombinant polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide of the invention may be provided in isolated or substantially isolated form. By substantially isolated, it is meant that there may be substantial, but not total, isolation of the polypeptide from any surrounding medium. The polynucleotides may be mixed with carriers or diluents which will not interfere with their intended use and still be regarded as substantially isolated. A nucleic acid sequence which “encodes” a selected polypeptide is a nucleic acid molecule which is transcribed (in the case of DNA) and translated (in the case of mRNA) into a polypeptide in vivo when placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a start codon at the 5' (amino) terminus and a translation stop codon at the 3' (carboxy) terminus. For the purposes of the invention, such nucleic acid sequences can include, but are not limited to, cDNA from viral, prokaryotic or eukaryotic mRNA, genomic sequences from viral or prokaryotic DNA or RNA, and even synthetic DNA sequences. A transcription termination sequence may be located 3' to the coding sequence. Representative polynucleotides which encode examples of a heavy chain or light chain amino acid sequence of an antibody may comprise or consist of any one of the nucleotide sequences disclosed herein, for example the sequences set out in Tables A and B. A suitable polynucleotide sequence may alternatively be a variant of one of these specific polynucleotide sequences. For example, a variant may be a substitution, deletion or addition variant of any of the above nucleic acid sequences. A variant polynucleotide may comprise 1, 2, 3, 4, 5, up to 10, up to 20, up to 30, up to 40, up to 50, up to 75 or more nucleic acid substitutions and / or deletions from the sequences given in the sequence listing. Suitable variants may be at least 70% homologous to a polynucleotide of any one of nucleic acid sequences disclosed herein, preferably at least 80 or 90% and more preferably at least 95%, 97% or 99% homologous thereto. Preferably homology and identity at these levels is present at least with respect to the coding regions of the polynucleotides. Methods of measuring homology are well known in the art and it will be understood by those of skill in the art that in the present context, homology is calculated on the basis of nucleic acid identity. Such homology may exist over a region of at least 15, preferably at least 30, for instance at least 40, 60, 100, 200 or more contiguous nucleotides. Such homology may exist over the entire length of the unmodified polynucleotide sequence. Methods of measuring polynucleotide homology or identity are known in the art. For example the UWGCG Package provides the BESTFIT program which can be used to calculate homology (e.g. used on its default settings) (Devereux et al, 1984; the disclosures of which are incorporated herein by reference). The PILEUP and BLAST algorithms can also be used to calculate homology or line up sequences (typically on their default settings), for example as described in Altschul, 1993; Altschul et al, 1990, the disclosures of which are incorporated herein by reference). Software for performing BLAST analysis is publicly available through the National Centre for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). This algorithm involves first identifying high scoring sequence pair (HSPs) by identifying short words of length W in the query sequence that either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighbourhood word score threshold (Altschul et al, supra). These initial neighbourhood word hits act as seeds for initiating searches to find HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Extensions for the word hits in each direction are halted when: the cumulative alignment score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The BLAST program uses as defaults a word length (W) of 11, the BLOSUM62 scoring matrix (see Henikoff & Henikoff, 1992; the disclosures of which are incorporated herein by reference) alignments (B) of 50, expectation (E) of 10, M=5, N=4, and a comparison of both strands. The BLAST algorithm performs a statistical analysis of the similarity between two sequences; see e.g. Karlin & Altschul, 1993; the disclosures of which are incorporated herein by reference. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a sequence is considered similar to another sequence if the smallest sum probability in comparison of the first sequence to the second sequence is less than about 1, preferably less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001. The homologue may differ from a sequence in the relevant polynucleotide by less than 3, 5, 10, 15, 20 or more mutations (each of which may be a substitution, deletion or insertion). These mutations may be measured over a region of at least 30, for instance at least 40, 60 or 100 or more contiguous nucleotides of the homologue. In one embodiment, a variant sequence may vary from the specific sequences given in the sequence listing by virtue of the redundancy in the genetic code. The DNA code has 4 primary nucleic acid residues (A, T, C and G) and uses these to “spell” three letter codons which represent the amino acids the proteins encoded in an organism’s genes. The linear sequence of codons along the DNA molecule is translated into the linear sequence of amino acids in the protein(s) encoded by those genes. The code is highly degenerate, with 61 codons coding for the 20 natural amino acids and 3 codons representing “stop” signals. Thus, most amino acids are coded for by more than one codon - in fact several are coded for by four or more different codons. A variant polynucleotide of the invention may therefore encode the same polypeptide sequence as another polynucleotide of the invention, but may have a different nucleic acid sequence due to the use of different codons to encode the same amino acids. A polypeptide may thus be produced from or delivered in the form of a polynucleotide which encodes, and is capable of expressing, it. Polynucleotides can be synthesised according to methods well known in the art, as described by way of example in Green & Sambrook (2012, Molecular Cloning - a laboratory manual, 4th edition; Cold Spring Harbor Press; the disclosures of which are incorporated herein by reference). A further aspect of the invention includes a kit comprising a vector (such as an expression vector) comprising a first isolated nucleic acid molecule encoding a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and: (i) a PD-1 inhibitor; and / or (ii) a second isolated nucleic acid molecule encoding an antibody or antigen binding fragment thereof that specifically binds to PD-1 or PD-L1 or a component polypeptide chain thereof, In an embodiment, the first isolated nucleic acid is as described in relation the previous aspect. The nucleic acid molecules may be provided in the form of an expression cassette which includes control sequences operably linked to the inserted sequence, thus allowing for expression of the polypeptide of the invention in vivo. These expression cassettes, in turn, are typically provided within vectors (e.g., plasmids or recombinant viral vectors). Such an expression cassette may be administered directly to a host subject. Alternatively, a vector comprising a polynucleotide of the invention may be administered to a host subject. Preferably the polynucleotide is prepared and / or administered using a genetic vector. A suitable vector may be any vector which is capable of carrying a sufficient amount of genetic information, and allowing expression of a polypeptide of the invention. The kit of the invention may include expression vectors that comprise the first isolated nucleic acid. Such expression vectors are routinely constructed in the art of molecular biology and may for example involve the use of plasmid DNA and appropriate initiators, promoters, enhancers and other elements, such as for example polyadenylation signals which may be necessary, and which are positioned in the correct orientation, in order to allow for expression of a peptide of the invention. Other suitable vectors would be apparent to persons skilled in the art (see Green & Sambrook, supra). A further aspect of the invention includes a kit comprising a recombinant host cell (such as a mammalian cell, e.g. human cell, or Chinese hamster ovary cell, e.g. CHOK1SV cells) comprising a first nucleic acid molecule encoding a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and: (i) a PD-1 inhibitor; and / or (ii) a second isolated nucleic acid molecule encoding an antibody or antigen binding fragment thereof that specifically binds to PD-1 or PD-L1 or a component polypeptide chain thereof. In an embodiment, the first isolated nucleic acid is as described in relation the previous aspect. The recombinant host cells that have been modified to express the bispecific polypeptide or component parts thereof. Such cells include transient, or preferably stable higher eukaryotic cell lines, such as mammalian cells or insect cells, lower eukaryotic cells, such as yeast or prokaryotic cells such as bacterial cells. Particular examples of cells which may be modified by insertion of vectors or expression cassettes encoding for a polypeptide of the invention include mammalian human embryonic kidney (HEK) (for example, HEK293T), CHO, HeLa, NS0 and COS cells. Preferably the cell line selected will be one which is not only stable, but also allows for mature glycosylation and cell surface expression of a polypeptide. Such cell lines may be cultured using routine methods to produce a bispecific polypeptide, or may be used therapeutically or prophylactically to deliver antibodies to a subject. Alternatively, polynucleotides, expression cassettes or vectors of the invention may be administered to a cell from a subject ex vivo and the cell then returned to the body of the subject. In one embodiment, the first isolated nucleic acid molecule encodes an antibody heavy chain or variable region thereof. In one embodiment, the first isolated nucleic acid molecule encodes an antibody light chain or variable region thereof. By “nucleic acid molecule” we include DNA (e.g. genomic DNA or complementary DNA) and mRNA molecules, which may be single- or double-stranded. By “isolated” we mean that the nucleic acid molecule is not located or otherwise provided within a cell. In one embodiment, the nucleic acid molecule is a cDNA molecule. It will be appreciated by persons skilled in the art that the nucleic acid molecule may be codon-optimised for expression of the antibody polypeptide in a particular host cell, e.g. for expression in human cells (for example, see Angov, 2011, the disclosures of which are incorporated herein by reference). Methods of production As described earlier, the second aspect of the invention relates to a pharmaceutical composition comprising an effective amount of: (a) a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) a PD-1 inhibitor, wherein the PD-1 inhibitor is formulated for parenteral delivery. In an embodiment, the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier. It will be appreciated by persons skilled in the art that additional compounds may also be included in the pharmaceutical compositions, including, chelating agents such as EDTA, citrate, EGTA or glutathione. The pharmaceutical compositions may be prepared in a manner known in the art that is sufficiently storage stable and suitable for administration to humans and animals. For example, the pharmaceutical compositions may be lyophilised, e.g. through freeze drying, spray drying, spray cooling, or through use of particle formation from supercritical particle formation. By “pharmaceutically acceptable" we mean a non-toxic material that does not decrease the effectiveness of the CD40 and CEA-binding activity of the bispecific polypeptide and / or the effectiveness of the PD-1 or PD-L1 binding activity of the PD-1 inhibitor. Such pharmaceutically acceptable buffers, carriers or excipients are well-known in the art (see Remington's Pharmaceutical Sciences, 18th edition, A.R Gennaro, Ed., Mack Publishing Company (1990) and handbook of Pharmaceutical Excipients, 3rd edition, A. Kibbe, Ed ., Pharmaceutical Press (2000), the disclosures of which are incorporated herein by reference). The term "buffer" is intended to mean an aqueous solution containing an acid-base mixture with the purpose of stabilising pH. Examples of buffers are Trizma, Bicine, Tricine, MOPS, MOPSO, MOBS, Tris, Hepes, HEPBS, MES, phosphate, carbonate, acetate, citrate, glycolate, lactate, borate, ACES, ADA, tartrate, AMP, AMPD, AMPSO, BES, CABS, cacodylate, CHES, DIPSO, EPPS, ethanolamine, glycine, HEPPSO, imidazole, imidazolelactic acid, PIPES, SSC, SSPE, POPSO, TAPS, TABS, TAPSO and TES. The term "diluent" is intended to mean an aqueous or non-aqueous solution with the purpose of diluting the polypeptide in the pharmaceutical preparation. The diluent may be one or more of saline, water, polyethylene glycol, propylene glycol, ethanol or oils (such as safflower oil, corn oil, peanut oil, cottonseed oil or sesame oil). The term "adjuvant" is intended to mean any compound added to the formulation to increase the biological effect of the bispecific polypeptide and / or the PD-1 inhibitor. The adjuvant may be one or more of zinc, copper or silver salts with different anions, for example, but not limited to fluoride, chloride, bromide, iodide, thiocyanate, sulfite, hydroxide, phosphate, carbonate, lactate, glycolate, citrate, borate, tartrate, and acetates of different acyl composition. The adjuvant may also be cationic polymers such as cationic cellulose ethers, cationic cellulose esters, deacetylated hyaluronic acid, chitosan, cationic dendrimers, cationic synthetic polymers such as poly(vinyl imidazole), and cationic polypeptides such as polyhistidine, polylysine, polyarginine, and peptides containing these amino acids. The excipient may be one or more of carbohydrates, polymers, lipids and minerals. Examples of carbohydrates include lactose, glucose, sucrose, mannitol, and cyclodextrines, which are added to the composition, e.g. for facilitating lyophilisation. Examples of polymers are starch, cellulose ethers, cellulose carboxymethylcellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, ethylhydroxyethyl cellulose, alginates, carageenans, hyaluronic acid and derivatives thereof, polyacrylic acid, polysulphonate, polyethyleneglycol / polyethylene oxide, polyethyleneoxide / polypropylene oxide copolymers, polyvinylalcohol / polyvinylacetate of different degree of hydrolysis, and polyvinylpyrrolidone, all of different molecular weight, which are added to the composition, e.g., for viscosity control, for achieving bioadhesion, or for protecting the lipid from chemical and proteolytic degradation. Examples of lipids are fatty acids, phospholipids, mono-, di-, and triglycerides, ceramides, sphingolipids and glycolipids, all of different acyl chain length and saturation, egg lecithin, soy lecithin, hydrogenated egg and soy lecithin, which are added to the composition for reasons similar to those for polymers. Examples of minerals are talc, magnesium oxide, zinc oxide and titanium oxide, which are added to the composition to obtain benefits such as reduction of liquid accumulation or advantageous pigment properties. The bispecific polypeptide and / or PD-1 inhibitor may be formulated into any type of pharmaceutical composition known in the art to be suitable for the delivery thereof. The PD-1 inhibitor is formulated for parenteral administration. In one embodiment, the pharmaceutical compositions of the invention may be in the form of a liposome, in which the bispecific polypeptide and / or the PD-1 inhibitor are combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids, which exist in aggregated forms as micelles, insoluble monolayers and liquid crystals. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Suitable lipids also include the lipids above modified by poly(ethylene glycol) in the polar headgroup for prolonging bloodstream circulation time. Preparation of such liposomal formulations can be found in for example US 4,235,871, the disclosures of which are incorporated herein by reference. The pharmaceutical compositions of the invention may also be in the form of biodegradable microspheres. Aliphatic polyesters, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), copolymers of PLA and PGA (PLGA) or poly(caprolactone) (PCL), and polyanhydrides have been widely used as biodegradable polymers in the production of microspheres. Preparations of such microspheres can be found in US 5,851,451 and in EP 0 213303, the disclosures of which are incorporated herein by reference. In a further embodiment, the pharmaceutical compositions of the invention are provided in the form of polymer gels, where polymers such as starch, cellulose ethers, cellulose carboxymethylcellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, ethylhydroxyethyl cellulose, alginates, carageenans, hyaluronic acid and derivatives thereof, polyacrylic acid, polyvinyl imidazole, polysulphonate, polyethyleneglycol / polyethylene oxide, polyethyleneoxide / polypropylene oxide copolymers, polyvinylalcohol / polyvinylacetate of different degree of hydrolysis, and polyvinylpyrrolidone are used for thickening of the solution containing the agent. The polymers may also comprise gelatin or collagen. Alternatively, the polypeptide may simply be dissolved in saline, water, polyethylene glycol, propylene glycol, ethanol or oils (such as safflower oil, corn oil, peanut oil, cottonseed oil or sesame oil), tragacanth gum, and / or various buffers. It will be appreciated that the pharmaceutical compositions of the invention may include ions and a defined pH for potentiation of action of the active polypeptide. Additionally, the compositions may be subjected to conventional pharmaceutical operations such as sterilisation and / or may contain conventional adjuvants such as preservatives, stabilisers, wetting agents, emulsifiers, buffers, fillers, etc. The pharmaceutical compositions according to the invention may be administered via any suitable route known to those skilled in the art. Thus, possible routes of administration include parenteral (intravenous, subcutaneous, intratumoral and intramuscular), topical, ocular, nasal, pulmonar, buccal, oral, parenteral, vaginal and rectal. Also administration from implants is possible. Preferably, the administration route is parenteral. Most preferably, the administration route is intravenous, subcutaneous or intratumoral. In one preferred embodiment, the pharmaceutical compositions are administered parenterally, for example, intravenously, intracerebroventricularly, intraarticularly, intra-arterially, intraperitoneally, intrathecally, intraventricularly, intrasternally, intracranially, intramuscularly or subcutaneously, or they may be administered by infusion techniques. They are conveniently used in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solutions should be suitably buffered (preferably to a pH of from 3 to 9), if necessary. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the art. Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. Thus, the pharmaceutical compositions of the invention are particularly suitable for parenteral, e.g. intravenous, administration. Alternatively, the pharmaceutical compositions may be administered intranasally or by inhalation (for example, in the form of an aerosol spray presentation from a pressurised container, pump, spray or nebuliser with the use of a suitable propellant, such as dichlorodifluoromethane, trichlorofluoro-methane, dichlorotetrafluoro-ethane, a hydrofluoroalkane such as 1,1,1,2-tetrafluoroethane (HFA 134A3 or 1,1,1,2,3,3,3- heptafluoropropane (HFA 227EA3), carbon dioxide or other suitable gas). In the case of a pressurised aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. The pressurised container, pump, spray or nebuliser may contain a solution or suspension of the active polypeptide, e.g. using a mixture of ethanol and the propellant as the solvent, which may additionally contain a lubricant, e.g. sorbitan trioleate. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated to contain a powder mix of a compound of the invention and a suitable powder base such as lactose or starch. The pharmaceutical compositions will be administered to a patient in a pharmaceutically effective dose. A ‘therapeutically effective amount’, or ‘effective amount’, or ‘therapeutically effective’, as used herein, refers to that amount which provides a therapeutic effect for a given condition and administration regimen. This is a predetermined quantity of active material calculated to produce a desired therapeutic effect in association with the required additive and diluent, i.e. a carrier or administration vehicle. Further, it is intended to mean an amount sufficient to reduce and most preferably prevent, a clinically significant deficit in the activity, function and response of the host. Alternatively, a therapeutically effective amount is sufficient to cause an improvement in a clinically significant condition in a host. As is appreciated by those skilled in the art, the amount of a compound may vary depending on its specific activity. Suitable dosage amounts may contain a predetermined quantity of active composition calculated to produce the desired therapeutic effect in association with the required diluent. In the methods and use for manufacture of compositions of the invention, a therapeutically effective amount of the active component is provided. A therapeutically effective amount can be determined by the ordinary skilled medical or veterinary worker based on patient characteristics, such as age, weight, sex, condition, complications, other diseases, etc., as is well known in the art. The administration of the pharmaceutically effective dose can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administrations of subdivided doses at specific intervals. Alternatively, the dose may be provided as a continuous infusion over a prolonged period. Particularly preferred compositions are formulated for systemic administration. The composition may preferably be formulated for sustained release over a period of time. Thus the composition may be provided in or as part of a matrix facilitating sustained release. Preferred sustained release matrices may comprise a montanide or DŽ-polyglutamic acid (PGA) nanoparticles. The bispecific polypeptides can be formulated at various concentrations, depending on the efficacy / toxicity of the polypeptide being used. For example, the formulation may comprise the active polypeptide at a concentration of between 0.1 μM and 1 mM, more preferably between 1 μM and 500 μM, between 500 μM and 1 mM, between 300 μM and 700 μM, between 1 μM and 100 μM, between 100 μM and 200 μM, between 200 μM and 300 μM, between 300 μM and 400 μM, between 400 μM and 500 μM, between 500 μM and 600 μM, between 600 μM and 700 μM, between 800 μM and 900 μM or between 900 μM and 1 mM. Typically, the formulation comprises the active polypeptide at a concentration of between 300 μM and 700 μM. Typically, the therapeutic dose of the bispecific polypeptide (with or without a therapeutic moiety) in a human patient will be in the range of 100 μg to 700 mg per administration (based on a body weight of 70 kg). For example, the maximum therapeutic dose may be in the range of 0.1 to 20 mg / kg per administration, e.g. between 0.1 and 5 mg / kg or between 1 and 5 mg / kg or between 0.1 and 2 mg / kg. It will be appreciated that such a dose may be administered at different intervals, as determined by the oncologist / physician; for example, a dose may be administered daily, twice-weekly, weekly, bi-weekly or monthly. For example, the combination therapies or pharmaceutical compositions of the invention may be administered in combination with a further immunotherapeutic agent that binds a target selected from the group consisting of VGFR, EGFR, HER2, CTLA-4, CD137, OX40, GITR, LAG3, TIM3, CD27, VISTA and KIR. Thus, the invention encompasses combination therapies or pharmaceutical compositions comprising a bispecific polypeptide of the invention and a PD-1 inhibitor together with a further immunotherapeutic agent, effective in the treatment of cancer and / or a tumour, which specifically binds to an immune checkpoint molecule. It will be appreciated that the therapeutic benefit of the further immunotherapeutic agent may be mediated by attenuating the function of an inhibitory immune checkpoint molecule and / or by activating the function of a stimulatory immune checkpoint or co- stimulatory molecule. In one embodiment, the further immunotherapeutic agent is selected from the group consisting of: (a) an immunotherapeutic agent that inhibits the function of CTLA-4; (b) an immunotherapeutic agent that activates the function of CD137; (c) an immunotherapeutic agent that binds activates the function of OX40; (d) an immunotherapeutic agent that inhibits the function of LAG3; (e) an immunotherapeutic agent that inhibits the function of TIM3; (f) an immunotherapeutic agent that inhibits the function of VISTA; (g) an immunotherapeutic agent that inhibits the function of VGFR; (h) an immunotherapeutic agent that inhibits the function of EGFR; and (i) an immunotherapeutic agent that inhibits the function of HER2. In another embodiment, the further immunotherapeutic agent is a CTLA-4 inhibitor, such as an anti-CTLA-4 antibody or antigen-binding portion thereof. In a further embodiment, the further immunotherapeutic agent activates CD137, such as an agonistic anti-CD137 antibody or antigen-binding portion thereof. In a further embodiment, the further immunotherapeutic agent activates OX40, such as an agonistic anti-OX40 antibody or antigen-binding portion thereof. In a further embodiment, the further immunotherapeutic agent inhibits the function of LAG3, TIM3 or VISTA (Lines et al. 2014). In another embodiment, the further immunotherapeutic agent is a VGFR inhibitor, such as an anti-VGFR antibody or antigen-binding portion thereof. In a further embodiment, the further immunotherapeutic agent activates EGFR, such as an agonistic anti-EGFR antibody or antigen-binding portion thereof. In a further embodiment, the further immunotherapeutic agent activates HER2, such as an agonistic anti-HER2 antibody or antigen-binding portion thereof. It will be appreciated by persons skilled in the art that the presence of the a further immunotherapeutic agent (as detailed above) may provide a synergistic benefit in the treatment of a tumour in a subject. By “synergistic” we include that the therapeutic effect of the agents in combination (e.g. as determined by reference to the rate of growth or the size of the tumour) is greater than the additive therapeutic effect of the individual agents administered on their own. Such synergism can be identified by testing the active agents, alone and in combination, in a relevant cell line model of the solid tumour. Medical uses and methods The combination therapies and pharmaceutical compositions in accordance with the present invention may be used in therapy or prophylaxis. In therapeutic applications, polypeptides or compositions are administered to a subject already suffering from a disorder or condition, in an amount sufficient to cure, alleviate or partially arrest the condition or one or more of its symptoms. Such therapeutic treatment may result in a decrease in severity of disease symptoms, or an increase in frequency or duration of symptom-free periods. An amount adequate to accomplish this is defined as "therapeutically effective amount". In prophylactic applications, polypeptides or compositions are administered to a subject not yet exhibiting symptoms of a disorder or condition, in an amount sufficient to prevent or delay the development of symptoms. Such an amount is defined as a “prophylactically effective amount”. The subject may have been identified as being at risk of developing the disease or condition by any suitable means. A fourth aspect of the invention provides a combination therapy or pharmaceutical composition according to the first or second aspect of the invention for use in medicine. A further aspect provides a combination therapy or pharmaceutical composition according to the first or second aspect for use in treating cancer and / or a tumour. A cancer and / or a tumour may be referred to as a neoplastic disorder. In one embodiment, the combination therapy or pharmaceutical composition is for use in combination with one or more additional immunotherapeutic agents. In one embodiment, the one or more additional therapeutic agents is / are an immunotherapeutic agent that binds a target selected from the group consisting of VGFR, EGFR, HER2, CTLA-4, CD137, OX40, GITR, LAG3, TIM3, CD27, VISTA and KIR. In one embodiment, the bispecific polypeptide is for administration parenterally or systemically. As described above, a fifth aspect of the invention provides a method for the treatment of cancer and / or a tumour in a subject, comprising (a) administering to the subject an effective amount of a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) administering to the subject an effective amount of a PD-1 inhibitor, wherein the PD-1 inhibitor is administered parenterally. The bispecific polypeptide and / or PD-1 inhibitor may be as described in relation to the previous aspects of the invention. In an embodiment, the bispecific polypeptide and the PD-1 inhibitor are administered simultaneously or within 24 hours of each other. In an embodiment, the bispecific polypeptide and / or the PD-1 inhibitor are administered parenterally. In an embodiment, the administration is intravenous, subcutaneous or intratumoural. In an embodiment, the dose of PD-1 inhibitor is: (i) between approximately 1 and 100 mg / kg bodyweight of the patient, optionally wherein the dose of the PD-1 inhibitor is 1 mg / kg, 10 mg / kg, 20 mg / kg or 100 mg / kg; and / or (ii) between approximately 2 mg / ml and 200 mg / ml, optionally wherein the dose is 2mg / ml, 10 mg / ml, 25 mg / ml, 150 mg / ml or 200 mg / ml; optionally wherein the PD-1 inhibitor is administered in a single or divided doses. In one embodiment, the method comprises administering the bispecific polypeptide systemically. In one embodiment, the methods further comprise administering to the subject one or more additional therapeutic agents. By ‘treatment’ we include both therapeutic and prophylactic treatment of the patient. The term ‘prophylactic’ is used to encompass the use of an agent, or formulation thereof, as described herein which either prevents or reduces the likelihood of a neoplastic disorder, or the spread, dissemination, or metastasis of cancer cells in a patient or subject. The term ‘prophylactic’ also encompasses the use of an agent, or formulation thereof, as described herein to prevent recurrence of a neoplastic disorder in a patient who has previously been treated for the cancer and / or tumour. Preferably, the cancer and / or the tumour is a cancer and / or the tumour associated with CEA; for example, CEA expression. By “associated with CEA”, we include that the CEA is cancer and / or the tumour is caused by CEA and / or CEA is a marker for the cancer and / or the tumour. In one embodiment, the cancer and / or the tumour comprises target cells comprising expression of CEA. Preferably, the expression of CEA is an intermediate level of CEA expression or a high level of CEA expression. In one embodiment, the intermediate level of CEA expression is characterised by the target cell expressing about 10,000 or more CEA receptors per target cell; for example, about 11,000 or more; about 12,000 or more; about 13,000 or more; about 14,000 or more; about 15,000 or more; about 16,000 or more; about 17,000 or more; about 18,000 or more; about 19,000 or more; about 20,000 or more; about 25,000 or more; about 30,000 or more; about 35,000 or more; about 40,000 or more; about 50,000 or more; about 60,000 or more; about 70,000 or more; about 80,000 or more; about 90,000 or more; about 100,000 or more; about 125,000 or more; about 150,000 or more; or about 175,000 or more CEA receptors per target cell. In another embodiment, the intermediate level of CEA expression is characterised by the target cell expressing about 10,000 to about 200,000 CEA receptors per target cell; for example, about 20,000 to about 175,000 CEA receptors per target cell or 20,000 to about 200,000 CEA receptors per target cell or about 50,000 to about 175,000 CEA receptors per target cell or about 50,000 to about 200,000 CEA receptors per target cell. Preferably, the CEA receptors are CEACAM5 receptors. In one embodiment, the high level of CEA expression is characterised by the target cell expressing about 200,000 or more CEA receptors per target cell; for example, about 225,000 or more; about 250,000 or more; about 275,000 or more; about 300,000 or more; about 325,000 or more; about 350,000 or more; about 375,000 or more; about 400,000 or more; about 425,000 or more; about 450,000 or more; about 475,000 or more; about 500,000 or more; about 600,000 or more; about 700,000 or more; about 800,000 or more; about 900,000 or more; or about 1,000,000 CEA receptors per target cell, preferably about 300,000 of more CEA receptors per target cell. In another embodiment, the high level of CEA expression is characterised by the target cell expressing about 200,000 to about 1,000,000 CEA receptors per target cell; for example, about 200,000 to about 500,000 CEA receptors per target cell or about 300,000 to about 500,000 CEA receptors per target cell. Preferably, the CEA receptors are CEACAM5 receptors. In one embodiment, the cancer and / or the tumour does not comprise a cell with no or a low level of CEA expression. In one embodiment, the low level of CEA expression is characterised by the cell expressing about 10,000 or fewer CEA receptors per target cell; for example, about 9,000 or fewer; about 8,000 or fewer; about 7,000 or fewer; about 6,000 or fewer; about 5,000 or fewer; about 4,000 or fewer; about 3,000 or fewer; about 2,000 or fewer; or about 1,000 or fewer CEA receptors per cell. In one embodiment, the CEA is a tumor-associated CEA. Preferably, the CEA is a CEACAM. In one embodiment, the CEACAM is one or more selected from the listing consisting of: CEACAM1; CEACAM3; CEACAM4; CEACAM5; CEACAM6; CEACAM7; CEACAM8; CEACAM16; CEACAM18; CEACAM19; CEACAM20; and CEACAM21. It will be appreciated that the reference to the aforementioned CEACAM molecules includes splice variants. Preferably, the CEACAM is one or more selected from the listing consisting of: CEACAM1; CEACAM5; and CEACAM6. Preferably, the CEACAM is CEACAM1. Most preferably, the CEACAM is CEACAM5. In a preferred embodiment, B2 is capable of specifically binding to CEACAM5 but not other CEACAMs, particularly not CEACAM1. In one embodiment, the cancer and / or the tumour is one or more cancer and / or tumour selected from the list consisting of: prostate cancer and / or a prostate tumour; breast cancer and / or a breast tumour; lung cancer and / or a lung tumour; colorectal cancer and / or a colorectal tumour; melanomas; bladder cancer and / or a bladder tumour; brain / CNS cancer and / or a brain / CNS tumour; cervical cancer and / or a cervical tumour; oesophageal cancer and / or a oesophageal tumour; gastric cancer and / or a gastric tumour; head / neck cancer and / or a head / neck tumour; kidney cancer and / or a kidney tumour; liver cancer and / or a liver tumour; a carcinoma; leukaemia; lymphomas; ovarian cancer and / or an ovarian tumour; pancreatic cancer and / or a pancreatic tumour; tonsil cancer and / or a tonsil tumour; and sarcomas. Preferably, a carcinoma. Preferably, the one or more cancer and / or tumour selected from the list consisting of: breast cancer and / or a breast tumour; lung cancer and / or a lung tumour; colorectal cancer and / or a colorectal tumour; gastric cancer and / or a gastric tumour; and / or pancreatic cancer and / or a pancreatic tumour. In a preferred embodiment, the cancer and / or tumour is a colorectal cancer and / or a colorectal tumour. In a preferred embodiment, the cancer is a gastric cancer and / or a gastric tumour. In a preferred embodiment, the cancer and / or tumour is a tonsil cancer and / or a tonsil tumour. Preferably, the carcinoma is one or more carcinoma selected from the listing consisting of: gastric carcinoma; oesophageal carcinoma; colorectal carcinoma; pancreatic carcinoma; lung carcinoma; breast carcinoma; cervical carcinoma; cholangiocarcinoma; and medullary thyroid carcinoma. In a preferred embodiment, the carcinoma is a colorectal carcinoma. Preferably, the tumour is a solid tumour. In one embodiment, the non-cancer condition is a non-cancer condition is one associated with CEA; for example, CEA expression. By “associated with CEA”, we include that the CEA is non-cancer condition is caused by CEA and / or CEA is a marker for the non-cancer condition. In one embodiment, the non-cancer condition comprises target cells comprising expression of CEA. Preferably, the expression of CEA is an intermediate level of CEA expression or a high level of CEA expression, as discussed herein. Preferably, the one or more non-cancer condition is selected from the list consisting of: ulcerative colitis, pancreatitis; cirrhosis; COPD; Crohn's disease; and / or hypothyroidism. In one embodiment, the subject is human. Optimised RUBY™ format The bispecific polypeptide may comprise the optimised RUBY™ format, preferably wherein the bispecific polypeptide has specificity for a first antigen and a second antigen. In particular, the bispecific polypeptide may comprises: (a) an immunoglobulin molecule having specificity for a first antigen, the immunoglobulin molecule comprising a first heavy chain polypeptide and a first light chain polypeptide; and (b) at least one Fab fragment having specificity for a second antigen, the Fab fragment comprising a second heavy chain polypeptide and a second light chain polypeptide wherein the second light chain polypeptide is fused to the C-terminus of the first heavy chain polypeptide and wherein the bispecific antibody comprises one or more mutations discussed in relation to the optimised RUBY™ format to promote association of the polypeptide; in particular, of the first heavy chain polypeptide with the first light chain polypeptide and / or to promote association of the second heavy chain polypeptide with the second light chain polypeptide. The optimised RUBY™ format has the structure shown in Figure 23 with further optimised mutations, when compared to the RUBY™ format. As will be appreciated by the skilled person, technology relating to antibody format has wide applicability to a wide range of different target antigens. Although bispecific polypeptides in the “RUBY™ format” can be reproducibly produced with an excellent level of purity, bispecific polypeptides in the “optimised RUBY™ format” can be reproducibly produced at an even higher level of purity. Further, bispecific polypeptides in the “optimised RUBY™ format” have been engineered to carry a reduced risk of provoking immunogenic responses directed against the bispecific polypeptide itself. In one embodiment, the bispecific polypeptide comprises an immunoglobulin arranged as an antibody with two arms and therefore two binding sites for the first antigen, and two of the Fab fragments, each providing a binding site for the second antigen. Thus, there are two binding sites for the first antigen and two binding sites for the second antigen. The first antigen and / or second antigen are not CD40 and / or CEA. In a further preferred embodiment, the first antigen and / or second antigen are a protein and / or peptide that is not CD40 and / or CEA. In one embodiment, the one or more Fab fragment(s) is linked to the C-terminal end of the immunoglobulin via a linker. In one embodiment, the bispecific polypeptide is tetravalent, capable of binding bivalently to each of the two antigens. The optimised mutations are described below as “optimised mutation set 1” and “optimised mutation set 2” – including “set 2a” and / or “set 2b”. It will be appreciated by the skilled person various combinations of these optimised mutations could be used in a bispecific polypeptide, as well as in combination with any of the “RUBY™ format” mutations described above. It will also be appreciated that the variations of those mutations as described herein would also work. All mutations in variable domains (VH or VL) are numbered according to the IMGT numbering system, and all mutations in the constant domains are numbered according to the EU numbering system. Mutation set 1 - Mutations in the variable domain heavy (VH): T65E, T65A, T65I. Mutation set 2 - any individual and / or any combination of the mutations listed in set 2a and set 2b. Set 2a - mutations in the CH1: Y180A, Y180G, Y180I, Y180N, Y180S, Y180T, Y180V, or Y180W, and / or S183N or S183T, and / or V188G; preferably, Y180T. Set 2b - mutations in the CKappa domain: A111R, A111T, A111W or A111V, and / or T109P; preferably: T109P and / or A111V; and / or mutations in the variable domain light (VL): I126A, I126G, I126H, I126N, I126P, I126Q, I126S, or I126T. In one embodiment, the mutations are at positions selected from the group consisting of: (a) the T65 position in the VH (according to the IMGT numbering system); and / or (b) one or more of the following positions in the CH1: Y180; S183; and V188, preferably Y180 (according to the EU numbering system); and / or (c) one or more of the following positions in the CKappa domain: A111 and T109 (according to the EU or Kabat numbering systems); and / or (d) the I126 position in the VL (according to the IMGT numbering system). In a particular embodiment, the mutation is at the T65 position in the variable domain heavy (VH) (according to the IMGT numbering system). In a particular embodiment, the mutations are one or more of the following positions in the CH1: Y180; S183; and V188, preferably Y180 (according to the EU numbering system). In a particular embodiment, the mutations are one or more of the following positions in the CKappa domain: A111 and T109 (according to the EU or Kabat numbering systems); and / or the I126 position in the VL (according to the IMGT numbering system). In one embodiment, the mutations are selected from the group consisting of: (a) X65E / A / I in the VH (according to the IMGT numbering system); and / or (b) one or more of the following mutations in the CH1: X180A / G / I / N / S / T / V / W; X183N / T; and X188G; preferably, X180T (according to the EU numbering system); and / or (c) one or more of the following mutations in the C-Kappa domain: X111R / T / W / V; and X109P, preferably X111V and X109P (according to the EU or Kabat numbering systems); and / or (d) X126A / G / H / N / P / Q / S / T in the VL (according to the IMGT numbering system). *X refers to any amino acid In a particular embodiment, the mutation is X65E / A / I in the VH chain (according to the IMGT numbering system). *X refers to any amino acid In a particular embodiment, the mutation is one or more of the following mutations in the CH1: X180A / G / I / N / S / T / V / W; X183N / T; and X188G; preferably, X180T (according to the EU numbering system). *X refers to any amino acid In a particular embodiment, the mutation is one or more of the following mutations in the CKappa domain: X111R / T / W / V; and X109P, preferably X111V and X109P (according to the IMGT numbering system); and / or the mutation is X126A / G / H / N / P / Q / S / T in the VL (according to the IMGT numbering system). *X refers to any amino acid For example, the mutations may be selected from the group consisting of: (a) one or more of the following mutations in the VH: T65E; T65A; and T65I (according to the IMGT numbering system); and / or (b) one or more of the following mutations in the CH1: Y180A; Y180G; Y180I; Y180N; Y180S; Y180T; Y180V; Y180W; S183N; S183T; V188G, preferably Y180T (according to the EU numbering system); and / or (c) one or more of the following mutations in the CKappa domain: A111R; A111T; A111W; A111V; and T109P, preferably T109P and A111V (according to the EU numbering system); and / or (d) one or more of the following mutations in the VL: I126A; I126G; I126H; I126N; I126P; I126Q; I126S; and I126T (according to the IMGT numbering system). In a particular example, the mutations are one or more of the following mutations in the VH: T65E; T65A; and T65I (according to the IMGT numbering system). In a particular example, the mutations are one or more of the following mutations in the CH1: Y180A; Y180G; Y180I; Y180N; Y180S; Y180T; Y180V; Y180W; S183N; S183T; V188G, preferably Y180T (according to the EU numbering system). In a particular example, the mutations are one or more of the following mutations in the C-kappa domain: A111R; A111T; A111W; A111V; and T109P, preferably T109P and A111V (according to the EU or Kabat numbering systems); and / or one or more of the following mutations in the VL: I126A; I126G; I126H; I126N; I126P; I126Q; I126S; and I126T (according to the IMGT numbering system). As discussed above, any combination of the “RUBY™ format” mutations and “optimised RUBY™ format” mutations can be used in the same bispecific antibody, such as any one or more of the following “RUBY™ format” mutations in (a) to (d), or variations described herein, being combined with any one or more of the following “optimised RUBY™ format” mutations in (e) to (g), or variations described herein: (a) one or more of the following mutations in the CH1 domain: H168A, F170G and / or T187E (according to EU numbering system); (b) one or more of the following mutations in the CKappa domain: L135Y, S176W, S114A and / or N137K (according to EU or Kabat numbering systems) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, T114A and / or S137K (according to Kabat numbering system); (c) mutations in the VL: Q44R or Q44E (according to IMGT numbering system); ad (d) mutations in the VH: Q44E or Q44R (according to IMGT numbering system); (e) mutations in the VH: T65E, T65A or T65I (according to IMGT numbering system); (f) mutation in the CH1: Y180T (according to EU numbering system); and / or (g) mutations in the CKappa: T109P and / or A111V (according to EU numbering system). Accordingly, in a particular embodiment, a bispecific antibody with combined “RUBY™ format” mutations and “optimised RUBY™ format” mutations could include the following mutations: x one or more of the following mutations in the CH1 domain: H168A, F170G, Y180T and / or T187E (according to EU numbering system); x one or more of the following mutations in the CKappa domain: T109P, A111V, L135Y, S176W, S114A and / or N137K (according to EU or Kabat numbering systems) and / or one or more of the following mutations in the CLambda domain: L135Y, S176W, T114A and / or S137K (according to Kabat numbering system); x mutations in the VL: Q44R or Q44E (according to IMGT numbering system); and / or x one or more of the following mutations in the VH: Q44E or Q44R, and / or T65E, T65A or T65I (according to IMGT numbering system). The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge. The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” These, and other, embodiments of the invention will be better appreciated and understood when considered in conjunction with the above description and the accompanying drawings. It should be understood, however, that the above description, while indicating various embodiments of the invention and numerous specific details thereof, is given by way of illustration and not of limitation. Many substitutions, modifications, additions and / or rearrangements may be made within the scope of the invention without departing from the spirit thereof, and the invention includes all such substitutions, modifications, additions and / or rearrangements. The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. Brief description of figures Preferred, non-limiting examples which embody certain aspects of the invention will now be described, with reference to the following figures: Figure 1. ELISA analysis of 22 CEA antibodies isolated using phage displayed combined with next generation sequencing. Binders in IgG1 format were analysed for binding to human CEACAM5 (abbreviated CAM5) (diagonal bars) or human CEACAM1 (abbreviated CAM1) (back bars). Figure 2. Ability of CD40 and CEACAM5 targeting RUBY™ bsAbs to bind both antigens simultaneously, as measured by dual target ELISA. Panel A shows binding curves for Multi34, Multi35, Multi37 and Multi38. Panel B shows binding curves for Multi39, Multi40, Multi41 and Multi42, Panel C shows binding curves for Multi44, Multi45, Multi46 and Multi47. Lastly, Panel D shows binding curves for Multi48, Multi4 and AC_05339. Figure 3. Cross-reactivity of RUBY™ bsAbs (Mult34, Multi35, Multi37-Multi42, Multi44- Multi49) with CEA protein family members CEACAM1, 5, 6 and 8, evaluated in ELISA. Figure 4. Kinetic measurement in Octet of interaction between captured CD40 CEACAM5 targeting bispecific antibodies (Multi 34, Multi42, Multi46 and AC_5339) against soluble monomeric human CEACAM5 (at varying concentrations ranging between 100-1.6nM). Association was measured for 100 sec followed by dissociation for 100 sec into 1x kinetic buffer. Figure 5. Kinetic measurement of bispecific antibodies (at varying concentrations ranging between 50-0.8nM) in solution interacting with captured human CEACAM5- biotin in Octet. Association was measured for 100 sec followed by dissociation for 100 sec into kinetic buffer. Figure 6. Binding of CD40-CEACAM5 bispecific antibodies to CEACAM5-transfected CHO cells. Binding of CD40-CEA bispecific antibodies was detected by flow cytometry using fluorochrome-conjugated anti-human IgG. Panel A shows binding curves for Multi34 and Multi35. Panel B shows binding curves for Multi41, Multi42, Multi44 and ffAC_5339. Panel C shows binding curves for Multi46, Multi47, Multi48 and Multi49. Panel D shows binding curves for ffAC_5337 and AC_5339. Panel E shows binding curves for AC_05355 and AC_05339. Figure 7. Binding of CD40-CEACAM5 bispecific antibodies to CEACAM1-transfected CHO cells (A-D) and to CHO wt cells (F). Binding of CD40-CEACAM5 bispecific antibodies was detected by flow cytometry using fluorochrome-conjugated anti-human IgG. Figure 8. Binding of CD40-CEACAM5 bispecific antibodies to CEACAM5 expressing tumor cells. The tumor cell line MKN45, expressing high levels of CEACAM5A-C), LS174T expressing intermediate levels of CEACAM5 (D-E), and Lovo expressing low levels CEACAM5 (G-J). Binding of CD40-CEACAM5 bispecific antibodies was detected by flow cytometry using fluorochrome-conjugated anti-human IgG. Figure 9. Effect of the CD40-CEACAM5 bispecific antibodies on CD40 reporter cells cultured with titrated antibodies in the presence or absence of CEACAM5 expressed on CHO cells. The response was calculated as fold induction to background. Figure 10. Effect of the CD40-CEACAM5 bispecific antibodies on CD40 reporter cells when co-cultured with tumor cells with different CEACAM5 receptor density. CD40- CEACAM5 containing CD40 clone G12 (A-D), CEACAM5-CD40 containing CD40 clone G12 (E-H) and CD40-CEACAM5 containing CD40 clone 1132 (I-J). The response was calculated as fold induction to background. Figure 11. Effect of the CD40-CEACAM5 bispecific antibodies on CD40 reporter cells co- cultured with CEACAM5 expressing CHO cells and titrated antibodies in the presence or absence of soluble CEACAM5. The response was calculated as fold induction to background. Figure 12. Effect of the CD40-CEACAM5 bispecific antibodies on B cell activation. Primary human B cells were cultured with titrated antibodies in the presence or absence of CEACAM5 expressed on CHO cells. After 2 days, expression of CD86 on B cells was analyzed by FACS. Figure 13. Effect of the CD40-cCEACAM5 bispecific antibody AC_05355 on B cell activation in the presence of human or cynomolgus CEACAM5 transfected cells. Primary human B cells were cultured with titrated antibodies in the presence of human or cynomolgus CEACAM5 expressed on CHO cells. After 2 days, expression of CD86 on B cells was analyzed by FACS. The graph shows pooled results from 6 donors. Figure 14. BsAb AC_05339 (0.02nM) w / o crosslinking to CHO-CEACAM5 or CHO-wt cells, activating HEK Blue CD40LTMreporter cells in presence of Raji cells after 20h incubation in a Transwell system. Activation monitored as SEAP release into culture medium, measured with QuantiBlueTM. Mean +SD of triplicate. Figure 15. BsAb Multi34 (3-0.004nM, single sample) crosslinked to CHO-CEACAM5 cells activating HEK Blue CD40LTMreporter cells w / o of presence of Raji sink cells in a Transwell system. Activation monitored as release of SEAP into culture media following 20h culture, measured with QuantiBlueTM. Figure 16. BsAb Multi42 (3-0.004nM, single sample) crosslinked to CHO-CEACAM5 cells activating HEK Blue CD40LTMreporter cells w / o of presence of Raji sink cells in a Transwell system. Activation monitored as release of SEAP into culture media following 20h culture, measured with QuantiBlueTM. Figure 17. BsAb Multi46 (100-0.1nM, single sample) crosslinked to CHO-CEACAM5 cells activating HEK Blue CD40LTMreporter cells w / o of presence of Raji sink cells in a Transwell system. Activation monitored as release of SEAP into culture media following 20h culture, measured with QuantiBlueTM. Figure 18. Colocalization of tumor debris and Raji cells. Raji cells were incubated with CEACAM5 expressing MKN45 tumor debris and AC_05339 or the control antibody 1132 with a silenced Fc, more specifically of the IgG1 isotype and carrying the L234A and L235A mutations (the antibody is herein refer to 1132.m2). Images were captured with a Cytation5 live imaging system and the number of tumor debris colocalized with Raji cells after 4 h was analyzed using Gen5 software. Figure 19. MC38-CEACAM5 tumor growth and MC38-wt rechallenge. hCD40tg mice inoculated with MC38-CEACAM5 tumors were dosed with the indicated treatments on days 7, 10, and 13 post-inoculations. Tumors were frequently measured until the first mouse in any of the treatment groups reached a tumor volume above the ethical limit. Statistical analysis of tumor volumes on day 38 was performed using a Mann-Whitney test (n=10, * p<0.05). Naïve control hCD40tg mice or mice cured from MC38- CEACAM5 tumors by treatment with a CD40-CEACAM5 bsAb (complete responders) were inoculated with MC38-wt tumors (rechallenged). Tumors were frequently measured until the first mouse in any of the treatment groups reached a tumor volume above the ethical limit. Figure 20. Effect of the CD40-CEACAM5 bispecific antibody AC_05355 on B cell activation in the presence of cynomolgus CEACAM5 (cCEACAM5) transfected CHO cells. Primary cynomolgus B cells were cultured with titrated antibodies in the presence cCEACAM5 expressed on CHO cells. After 2 days, expression of CD86 on B cells was analyzed by FACS. The graph shows pooled data from 2 donors. Figure 21. MC38-CEACAM5 tumor growth. hCD40tg mice inoculated with MC38- CEACAM5 tumors were dosed with the indicated treatments on days 10, 13 and 16 post inoculation. Tumors were frequently measured until the first mouse in any of the treatment groups reached a tumor volume above the ethical limit. Statistical analysis of tumor volumes on day 17 was performed using a Mann-Whitney test (n=10, * p<0.05). Figure 22. This shows a schematic representation of the structure of exemplary formats for a bispecific antibody. In each format, the constant regions are shown as filled light grey; variable heavy chain regions VH1 are shown as chequered black and white; variable light chain regions VL1 are shown as filled white; variable heavy chain regions VH2 are shown as filled black; and variable light chain regions VL2 are shown as white with diagonal lines. CD40 binding domains (binding domain 1) are typically represented as a pair of a chequered black and white domain with a filled white domain (VH1 / VL1); CEA binding domains (binding domain 2) are typically represented as a pair of a filled black domain and a white domain with diagonal lines (VH2 / VL2). However, in all of the formats shown, it will be appreciated that binding domains 1 and 2 may be switched. That is, a CD40 binding domain may occur in a position shown in this figure for a CEA- binding domain, and vice versa. Figure 23. This shows an example composition of a bispecific antibody construct, in the RUBYTMformat. The bispecific antibody of Figure 21 is made up of three types of polypeptide chains: (1) IgG heavy chains (white) fused to Fab light chains (chequered) via a polypeptide linker. (2) IgG light chains (bricked) and (3) Fab heavy chains (black). Mutations are introduced in the interface between heavy and light chains. Figure 24. CD40xTAA bsAbs mediate localization of tumor debris to antigen presenting cells. The number of CEA+ tumor debris clustering with CD40+ cells was quantified after 8 hrs of culture using live cell imaging software. The graphs show the mean (+SD) of duplicate wells in one representative experiment of four (CEA). Figure 25. Dissociated cells from human colorectal cancer tumors were analyzed for: (left) their CEA-expression (gated on total viable cells), (middle) ability to provide cross-linking to CD40xCEA Neo-X-Prime bsAb in a CD40 reporter assay, and (right) CD83 upregulation following stimulation of the tumor infiltrating immune cells (gated on viable CD45+CD3-CD56- cells) using CD40xCEA Neo-X-Prime bsAb or isotypexCD40 bsAb (data from 1 representative experiment out of three). Figure 26. Simultaneous binding of CD40 and CEA by CD40xCEA bsAbs mediates activation of tonsillar cancer APCs in vitro. Human CD45+ HLA-DR+ CD3- cells from a tonsillar cancer biopsy were co-cultured with UV-irradiated CHO cells transfected with human CEA in the presence of CD40xCEA bsAb, CD40 mAb or isotype control. After 13 h culture, cells were harvested and the frequencies of CD86+ CD40+ cells were investigated using flow cytometry of CD19+ CD20+ B cells, CD14+ macrophages, CD1c+ cDC2s and XCR1+ cDC1s. Figure 27. Accumulation of the CD40xCEA bsAb, but not corresponding CD40 mAb, in CEA-expressing tumors. Human CD40 transgenic mice were inoculated with MC38- hCEA tumor cells (MC-38-CEA-2, Kerafast) s.c. and were administered with 100 μg anti-CD40 antibody or a molar equivalent dose (167 μg) CD40xCEA bsAb or Isotype bsAb i.p. on days 10 and 13. On day 14, tumors were dissected. Frozen tumor sections were stained for human IgG to assess accumulation of administered antibodies, and for CEA to assess CEA expression pattern in the tumors. Representative images of (A) IgG staining and (B) CEA staining are shown. The staining pattern obtained following treatment with CD40xCEA is significantly stronger than for the controls, and the staining pattern is consistent with the CEA-staining of the tumor. Figure 28. Cryo preserved tumors (B16.F10-hCD40+ # 6, 7 and 9 used as control, hereafter called B16 AND MB49 #2, 4 and 5) from human CD40 transgenic mice were analyzed. 8μm cryosections were prepared and stained. Mouse spleen was used as positive control. The sections were analyzed in a Leica DMRX-e microscope and representative photos were taken. A) representative images from MB49 tumors. B) The immunohistochemical staining was judged as follows; negative (0), few positive cells (1+), moderate numbers of positive cells (2+), high numbers of positive cells (3+) or very high numbers of positive cells (4+). The analysis shows that a marked higher degree of infiltrating T cells are seen in the MB49 tumors compared to the B16 tumors used as control. Antibodies used for staining: CD4: Rat IgG, Affymetrix,14- 00421:200, CD8 Rat IgG, Affymetrix,14-00811:200, CD3 Rabbit, Dako, A04521:100, CD45 Rat IgG, Biodesign 1:100. C) Immune cell population frequencies in MB49- EpCAM tumors, with similar in vivo growth and immune infiltration as MB49 tumors. Human CD40 transgenic mice were injected with MB49-hEpCAM cells (0,25x106) s.c. into the right flank in 100 ul of PBS. 12 days after tumor inoculation, tumors were dissected, dissociated and stained for flow cytometry analysis of immune cell content. The frequencies of NK cells (CD45+, CD11b-, CD19- MHC II-, TCRbeta-, NK1.1+), T cells (CD45+, CD11b-, CD19- MHC II-, TCRbeta+, NK1.1-), B cells (CD45+, Ly6G-, CD3-, NK1.1-, CD19+), monocytes / macrophages (CD45+, Ly6G-, CD3-, NK1.1-, CD64+) and DCs (CD45+, Ly6G-, CD3-, NK1.1-, CD64-, CD11c+, MHC II+) within the total viable CD45+ population was assessed. Figure 29. Data from NHP study. A) B cell activation of the cynoCEAxCD40 RUBY™ on cynomolgus and human B cells in the presence of CEA transfected cells (macaque CEA, NP_001040590.1). Primary cynomolgus B cells were cultured with titrated antibodies in the presence CEA expressed on CHO cells. After 2 days, expression of CD86 on B cells was analyzed by FACS. The graphs show pooled data from two cynomolgus and four human donors. The data demonstrate that CEAxCD40 bsAbs in the RUBY™ format induce upregulation of CD86 on cynomolgus and human B cells to a similar degree. The CEA-conditional activation of CD40 on cynomolgus B cells and human B cells is similar to what is observed with the human CEAxCD40 bsAb in RUBY ™ used for the in vitro assays. The cynoCEAxCD40 bsAb binds with similar affinity to human and cynomolgus monkey CEA (hCEA vs cCEA, right panel). In B) and C) key data from the toxicology assessment in cynomolgus monkey is presented. The cynoCEAxCD40 bispecific antibody was administered once weekly via intravenous infusion for 2 weeks to cynomolgus monkeys at two different dose levels (10 mg / kg and 37.5 mg / kg). One female and one male were evaluated at each dose level. B) Data on L-aspartate aminotransferase (ASAT) and L-alanine aminotransferase (ALAT) and C) levels of IL-6 and TNFalpha over time. In addition, plasma levels for the following cytokines were measured by a bead-based multiplex immunoassay: IL-2, IL-6, IL-8, IL-10, MCP-1, IFN-DŽ and TNF-Į. The conclusion from the study was that there were no findings associated with cyoCEAxCD40 bsAb at the evaluated dose levels. Figure 30. Structure of RUBY™ bsAb and binding of RUBY™ bsAb to their various antigen targets as measured by ELISA. (A) Chain 1 consists of the IgG heavy chain, a short polypeptide linker and the light chain of the additional Fab fragment, chain 2 is a light chain that binds to the VH and CH1 domains of the IgG part and chain 3 is a short heavy chain that binds to the light chain appended to the IgG. (B) Dual ELISA showing simultaneous binding of CD40xEpCAM RUBY™ bsAb to its respective antigen targets. ELISA plates were coated with human CD40, bsAb was added followed by detection using biotinylated EpCAM.(C) Dual ELISA showing simultaneous binding of CD40xCEA RUBY™ bsAb to its respective antigen targets. ELISA plates were coated with human CEACAM5, bsAb was added followed by detection using biotinylated CD40. (D) Mono ELISA showing binding of GFPxEpCAM control RUBY™ bsAb to human EpCAM. ELISA plates were coated with human EpCAM, bsAb was added followed by detection using goat anti human-kappa light chain-HRP. (E) Mono ELISA showing binding of cynoCEAxCD40 RUBY™ bsAb to human CD40. ELISA plates were coated with human CD40 followed by addition of cynoCEAxCD40 RUBY™ bsAb and detection using goat anti human-kappa light chain-HRP. (F). Mono ELISA showing binding of cynoCEAxCD40 RUBY™ bsAb to human CEACAM5. ELISA plates were coated with human CEA followed by addition of cynoCEAxCD40 RUBY™ bsAb and detection using goat anti human-kappa light chain-HRP. In summary, Bispecific antibodies were successfully generated in the RUBY™format and the generated bsAbs displayed good binding to their respective antigen targets as illustrated by the ELISA binding evaluations. Figure 31. MC38-CEACAM52 tumor growth and survival. hCD40tg mice inoculated with MC38-CEACAM5 2 tumors were dosed with the indicated treatments on days 7, 10, and 13 post-inoculation. Tumors were frequently measured, and the graphs shows the mean tumor volume (+SD) of each group until the first mouse in any of the treatment groups reached a tumor volume above the ethical limit, and the % surviving mice in each treatment group. Figure 32. Dissociated cells from human gastric cancer tumors were analyzed for: (left) their CEA-expression (gated on total viable cells), (middle) ability to provide cross- linking to CD40xCEA Neo-X-Prime bsAb (ffAC_05337) in a CD40 reporter assay, and (right, 1nM CD40xCEA) CD83 upregulation following stimulation of the tumor infiltrating immune cells (gated on viable CD45+CD3-CD56- cells) using CD40xCEA Neo-X-Prime bsAb or isotypexCD40 bsAb (data from 1 representative experiment out of four). Figure 33. Effect of the bispecific antibody ffAC_05337on CD40 reporter cells when co- cultured with tumor cells with different CEA receptor density in the presence and absence of soluble CEA. MKN45, CEA high expressing cells (A), LS174T, CEA intermediate expressing cells (B), HT29 and LOVO, CEA low expressing cells (C-D). The response was calculated as fold induction to background. Figure 34. Effect of the bispecific antibody ffAC_05337 on CD40 reporter cells co- cultured with CEA expressing CHO cells and titrated antibodies in the presence or absence of soluble CEA. The response was calculated as fold induction to background. Figure 35 shows T-cell activation by a CD40xCEA bispecific antibody (ffAC_05337) in combination with a PD-1 inhibitor (nivolumab) in a mixed lymphocyte reaction (MLR) assay with exhausted CD4 T cells. The additive effect of the individual monotherapies is marked with a dotted line. Figure 36 shows T-cell activation by a CD40xCEA bispecific antibody (ffAC_05337) in combination with a PD-1 inhibitor (nivolumab) in a mixed lymphocyte reaction (MLR) assay with exhausted CD8 T cells. The additive effect of the individual monotherapies is marked with a dotted line in Figures 36 B and D. Figure 37 shows T-cell activation by a CD40xCEA bispecific antibody (ffAC_05337) in combination with a PD-L1 inhibitor (atezolizumab) in a mixed lymphocyte reaction (MLR) assay with exhausted CD4 or CD8 T cells. The additive effect of the individual monotherapies is marked with a dotted line in Figures 37 B and C. Figure 38 shows the effect of CD40xCEA bispecific antibody (ffAC_05337) treatment on PD-1 and PD-L1 gene expression, compared to vehicle control. Figure 38A shows gene expression of CD274 (PD-L1) in sorted immune cells (CD45+Ly6G-) after treatment. Figure 38B shows gene expression of Pdcd1 (PD-1) in sorted immune cells (CD45+Ly6G-) after treatment. Figure 38C shows gene expression of CD274 (PD-L1) in whole tumors after treatment. Figure 38D shows gene expression of Pdcd1 (PD-1) in whole tumors after treatment. Figure 39 shows the number of PD-L1 expressing tumor infiltrating macrophages and dendritic cells per mg tumor after CD40xCEA bispecific antibody (ffAC_05337) treatment. Each dot represents one mouse, bar represents mean. Figure 40A shows the survival curve of MC38-CEACAM5 inoculated F1 hCD40tg×C57BL / 6 mice treated with vehicle, a CD40xCEA bispecific antibody (ffAC_05337), aPD-1 mAb or a combination of a CD40xCEA bispecific antibody (ffAC_05337) and aPD-1 mAb. N=9-10 / group. Figure 40B shows average tumor growth curve in mice treated with CD40xCEA bispecific antibody (ffAC_05337), aPD-1 mAb or a combination of CD40xCEA bispecific antibody (ffAC_05337) and aPD-1 mAb. Each line represents mean, and bars represent SEM. Mice sacrificed due to human end point are included in graph after end point, plotted as the same size as on the day they were sacrificed until no more mice remained in the group. N= 9-10 / group. Figure 41 shows the effect of 5 days of stimulation with a CD40xCEA bispecific antibody (ffAC_05337) and / or anti-PD1 (nivolumab) on dissociated cells from human gastric cancer tumors. Cells were analysed for CD25 upregulation on CD8+ T cells by flow cytometry. Depicted is the percentage of CD25+CD8 T cells (untreated sample of subtracted), mean ± SEM from 2 patient samples. Sequence Tables Table A – Binding domain B1 VL and VH amino acid (aa) and nucleotide (nt) sequences SEQ ANTIBODY REF TYPE SEQUENCE ID NO. 1 1132, light aa DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY chain VL (also QQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFT known as 1133) LTISSLQPEDFATYYCQQYGRNPPTFGQGTKLEIK 2 1132, light nt gatattcagatgacccagagcccgagcagcctgagcgcgagcg chain VL (also tgggcgatcgcgtgaccattacctgccgcgcgagccagagcatt known as 1133) agcagctatctgaactggtatcagcagaaaccgggcaaagcgc cgaaactgctgatttatgcggcgagcagcctgcagagcggcgtg ccgagccgctttagcggcagcggcagcggcaccgattttaccct gaccattagcagcctgcagccggaagattttgcgacctattattg ccagcagtatggccgcaacccgccgacctttggccagggcacca aactggaaattaaa 3 1132, heavy aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS chain VH WVRQAPGKGLEWVSGIGSYGGGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCARYVNFGMD YWGQGTLVTVSS 4 1132, heavy nt gaagtgcagctgctggaaagcggcggcggcctggtgcagccg chain VH ggcggcagcctgcgcctgagctgcgcggcgagcggctttacctt tagcagctatgcgatgagctgggtgcgccaggcgccgggcaaa ggcctggaatgggtgagcggcattggcagctatggcggcggca cctattatgcggatagcgtgaaaggccgctttaccattagccgcg ataacagcaaaaacaccctgtatctgcagatgaacagcctgcgc gcggaagataccgcggtgtattattgcgcgcgctatgtgaacttt ggcatggattattggggccagggcaccctggtgaccgtgagca gc 5 1150, light aa DIQMTQSPSSLSASVGDHVTITCRASQSISSYLNW chain VL (also YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDF known as 1151) TLTISSLQPEDFATYYCQQYGSAPPTFGQGTKLEIK 1150, light nt gatattcagatgacccagagcccgagcagcctgagcgcgagcg chain VL (also tgggcgatcatgtgaccattacctgccgcgcgagccagagcatt known as 1151) agcagctatctgaactggtatcagcagaaaccgggcaaagcgc cgaaactgctgatttatgcggcgagcagcctgcagagcggcgtg ccgagccgctttagcggcagcggcagcggcaccgattttaccct gaccattagcagcctgcagccggaagattttgcgacctattattg ccagcagtatggcagcgcgccgccgacctttggccagggcacc aaactggaaattaaa 1150, heavy aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS chain VH WVRQAPGKGLEWVSGIGGSSSYTSYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCARYYSYHMD YWGQGTLVTVSS 1150, heavy nt gaagtgcagctgctggaaagcggcggcggcctggtgcagccg chain VH ggcggcagcctgcgcctgagctgcgcggcgagcggctttacctt tagcagctatgcgatgagctgggtgcgccaggcgccgggcaaa ggcctggaatgggtgagcggcattggcggcagcagcagctata ccagctatgcggatagcgtgaaaggccgctttaccattagccgc gataacagcaaaaacaccctgtatctgcagatgaacagcctgcg cgcggaagataccgcggtgtattattgcgcgcgctattatagcta tcatatggattattggggccagggcaccctggtgaccgtgagca gc 1140, light aa DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY chain VL (also QQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFT known as 1135) LTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK 1140, light nt gatattcagatgacccagagcccgagcagcctgagcgcgagcg chain VL (also tgggcgatcgcgtgaccattacctgccgcgcgagccagagcatt known as 1135) agcagctatctgaactggtatcagcagaaaccgggcaaagcgc cgaaactgctgatttatgcggcgagcagcctgcagagcggcgtg ccgagccgctttagcggcagcggcagcggcaccgattttaccct gaccattagcagcctgcagccggaagattttgcgacctattattg ccagcagagctatagcaccccgtatacctttggccagggcacca aactggaaattaaa 1140, heavy aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS chain VH WVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCARGPVYSSV FDYWGQGTLVTVSS 1140, heavy nt gaagtgcagctgctggaaagcggcggcggcctggtgcagccg chain VH ggcggcagcctgcgcctgagctgcgcggcgagcggctttacctt tagcagctatgcgatgagctgggtgcgccaggcgccgggcaaa ggcctggaatgggtgagcgcgattagcggcagcggcggcagc acctattatgcggatagcgtgaaaggccgctttaccattagccgc gataacagcaaaaacaccctgtatctgcagatgaacagcctgcg cgcggaagataccgcggtgtattattgcgcgcgcggcccggtgt atagcagcgtgtttgattattggggccagggcaccctggtgacc gtgagcagc 1107, light aa DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY chain VL (also QQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFT known as 1108) LTISSLQPEDFATYYCQQYGVYPFTFGQGTKLEIK 1107, light nt gatattcagatgacccagagcccgagcagcctgagcgcgagcg chain VL (also tgggcgatcgcgtgaccattacctgccgcgcgagccagagcatt known as 1108) agcagctatctgaactggtatcagcagaaaccgggcaaagcgc cgaaactgctgatttatgcggcgagcagcctgcagagcggcgtg ccgagccgctttagcggcagcggcagcggcaccgattttaccct gaccattagcagcctgcagccggaagattttgcgacctattattg ccagcagtatggcgtgtatccgtttacctttggccagggcaccaa actggaaattaaa 1107, heavy aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS chain VH WVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCARRVWGFDY WGQGTLVTVSS 1107, heavy nt gaagtgcagctgctggaaagcggcggcggcctggtgcagccg chain VH ggcggcagcctgcgcctgagctgcgcggcgagcggctttacctt tagcagctatgcgatgagctgggtgcgccaggcgccgggcaaa ggcctggaatgggtgagcgcgattagcggcagcggcggcagc acctattatgcggatagcgtgaaaggccgctttaccattagccgc gataacagcaaaaacaccctgtatctgcagatgaacagcctgcg cgcggaagataccgcggtgtattattgcgcgcgccgcgtgtggg gctttgattattggggccagggcaccctggtgaccgtgagcag...

Claims

Claims 1. A combination therapy comprising: (a) a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) a PD-1 inhibitor, wherein the PD-1 inhibitor is formulated for parenteral delivery.

2. A combination therapy according to any one of the preceding claims, wherein the parenteral delivery comprises intravenous administration, subcutaneous administration, or intratumoural administration.

3. The combination therapy according to any preceding claim, wherein the first and / or second binding domains of the bispecific polypeptide are / is selected from the group consisting of antibodies and antigen-binding fragments thereof, and CD40 ligands.

4. The combination therapy according to Claim 3 wherein the antigen-binding fragment is selected from the group consisting of: Fv fragments (such as a single chain Fv fragment, or a disulphide-bonded Fv fragment), Fab-like fragments (such as a Fab fragment; a Fab’ fragment or a F(ab)2 fragment) and domain antibodies.

5. The combination therapy according to any one of the preceding claims wherein the bispecific polypeptide is a bispecific antibody.

6. The combination therapy according to any one of the preceding claims wherein the bispecific polypeptide has: (a) binding domain B1 and / or binding domain B2 is an intact IgG antibody; (b) binding domain B1 and / or binding domain B2 is an Fv fragment; (c) binding domain B1 and / or binding domain B2 is a Fab fragment; and / or (d) binding domain B1 and / or binding domain B2 is a single domain antibody.

7. The combination therapy according to Claim 6, wherein the bispecific polypeptide comprises a human Fc region or a variant of a said region, where the region is an IgG1, IgG2, IgG3 or IgG4 region, preferably an IgG1 or IgG4 region.

8. The combination therapy according to Claim 7, wherein the bispecific polypeptide comprises an Fc that exhibits no or very low affinity for Fc^R.

9. The combination therapy according to Claim 8, wherein the Fc region is a variant of a human IgG1 Fc region comprising a mutation at one or more of the following positions: L234, L235, P239, D265, N297 and / or P329.

10. The combination therapy according to Claim 9, wherein alanine is present at the mutated position(s).

11. The combination therapy according to Claim 10, wherein the Fc region is a variant of a human IgG1 Fc region comprising the double mutations L234A and L235A.

12. The combination therapy according to any one of Claims 5 to 11, wherein the bispecific polypeptide is selected from the groups consisting of: (a) bivalent bispecific antibodies, such as IgG-scFv bispecific antibodies (for example, wherein B1 is an intact IgG and B2 is an scFv attached to B1 at the N- terminus of a light chain and / or at the C-terminus of a light chain and / or at the N- terminus of a heavy chain and / or at the C-terminus of a heavy chain of the IgG, or vice versa); (b) monovalent bispecific antibodies, such as a ‘knob-in-hole’ bispecific antibody (for example, an scFv-KIH, scFv-KIHr, a BiTE-KIH or a BiTE- KIHr); (c) scFv2-Fc bispecific antibodies; (d) BiTE / scFv2 bispecific antibodies; (e) DVD-Ig bispecific antibodies; (f) DART-based bispecific antibodies (for example, DART2-Fc or DART); (g) DNL-Fab3 bispecific antibodies; and (h) scFv-HSA-scFv bispecific antibodies.

13. The combination therapy according to Claim 12, wherein the bispecific polypeptide is an IgG-scFv bispecific antibody.

14. The combination therapy according to any one of the preceding claims, wherein binding domain B1 and binding domain B2 are fused directly to each other.

15. The combination therapy according to any one of the preceding claims, wherein binding domain B1 and binding domain B2 are joined via a polypeptide linker.

16. The combination therapy according to Claim 15, wherein the linker is selected from the group consisting of the amino acid sequence SGGGGSGGGGS (SEQ ID NO: 337), SGGGGSGGGGSAP (SEQ ID NO: 338), NFSQP (SEQ ID NO: 339), KRTVA (SEQ ID NO: 340), GGGSGGGG (SEQ ID NO: 341), GGGGSGGGGS (SEQ ID NO: 342), GGGGSGGGGSGGGGS (SEQ ID NO: 343), GSTSGSGKPGSGEGSTKG (SEQ ID NO: 344), THTCPPCPEPKSSDK (SEQ ID NO: 345), GGGS (SEQ ID NO: 346), EAAKEAAKGGGGS (SEQ ID NO: 347), EAAKEAAK (SEQ ID NO: 348), or (SG)m, where m = 1 to 7.

17. The combination therapy according to any one of the preceding claims, wherein one of B1 or B2 is an immunoglobulin molecule, and one of B1 or B2 is a Fab fragment, wherein the Fab fragment is fused to the C-terminus of the heavy chain of the immunoglobulin via the light chain of the Fab fragment.

18. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide comprises one or more mutations to promote association of the heavy chain polypeptide of the immunoglobulin with the light chain polypeptide of the immunoglobulin and / or to promote association of the heavy chain polypeptide of the Fab with the light chain polypeptide of the Fab.

19. The combination therapy according to Claim 18, wherein the one or more mutations prevent the formation of aggregates and a Fab by-product.

20. The combination therapy according to Claim 18 or 19, wherein the mutations prevent formation of aggregates and Fab by-products by generating steric hindrance and / or incompatibility between charges.

21. The combination therapy according to any one of Claims 18 to 20, wherein the bispecific polypeptide comprises one or more mutation pairs each comprising two functionally compatible mutations.

22. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide can modulate the activity of and / or activate myeloid cells.

23. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide is incapable of inducing antibody-dependent cell cytotoxicity(ADCC), antibody-dependent cellular phagocytosis (ADCP) and / or complement- dependent cytotoxicity (CDC).

24. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide is capable of inducing tumour immunity.

25. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide is capable of inducing: (a) tumour-specific immune activation; and / or (b) activation of dendritic cells; and / or (c) internalisation of associated tumour debris and / or extracellular vesicles containing CEA antigens as well as tumour neoantigens; and / or (d) cross-presentation of peptides derived from internalised tumour antigens on MHC; and / or (e) priming and activation of effector T cells; and / or (f) direct tumoricidal effects, selected from the list consisting of: apoptosis, necroptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement- dependent cytotoxicity (CDC).

26. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide is capable of: (a) activation of a B-cell, in the presence of a CEA; and / or (b) activation of dendritic cells in the presence of CEA; and / or (c) capable of increased dendritic cell cross-presentation of neoantigens; and / or (d) inducing proliferation of neoantigen specific T cells.

27. The combination therapy according to any one of the preceding claims, wherein the bispecific polypeptide promotes uptake of tumor derived material, derived from tumor cells overexpressing CEA.

28. The combination therapy according to Claim 26, wherein the B-cell activation is characterised by CD86 upregulation.

29. The combination therapy according to any one of the preceding claims wherein binding domain B1 binds to human CD40 with a KD of less than 2x10-7M or less than 1.5x10-7M or less than 8.5x10-8M or less than 8x10-8M or less than 7.5x10-8M or lessthan 7x10-8M or less than 9x10-8M or less than 9x10-9M or less than 5x10-10M or less than 3x10-10M, preferably less than 8.5x10-8M, more preferably less than 5x10-10M or less than 3x10-10M.

30. The combination therapy according to any one of the preceding claims, wherein binding domain B1 comprises one or more heavy chain CDR sequences selected from those in Table C(1) and / or wherein binding domain B1 comprises one or more light chain CDR sequences selected from those in Table C(2).

31. The combination therapy according to any one of the preceding claims, wherein binding domain B1 comprises one, two or three light chain CDR sequences from a particular row for an individual antibody reference in Table C(2), and / or one, two or three heavy chain CDR sequences from the corresponding row for the antibody with the same reference in Table C(1).

32. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises all three heavy chain CDR sequences of a particular antibody reference as shown in Table C(1), and / or all three light chain CDR sequences of an antibody reference as shown in Table C(2), or wherein binding domain B1 comprises a heavy chain VH sequence and / or a light chain VL sequence as shown in Table A.

33. The combination therapy according to any one of the preceding claims, wherein B1 comprises any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which consists of the sequence “G, F, T, F, S, S, Y, A”; (b) a heavy chain CDR2 sequence which is 8 amino acids in length and comprises the consensus sequence: “I, G / S, S / G, Y / S, G / S, G / S, G / Y / S, T”; (c) a heavy chain CDR3 sequence which is 9 to 12 amino acids in length and which comprises the consensus sequence of : “A, R, Y / R / G, Y / P / V / -, N / S / V, F / Y / W, G / H / S, - / S, - / V, M / F, D, Y” (d) a light chain CDR1 sequence which consists of the sequence: “Q, S, I, S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which is 9 amino acids in length and comprises the consensus sequence: “Q, Q, Y / S, G / Y, R / S / V, N / A / Y / T, P, P / F / Y, T”.

34. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises: (a) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1132 / 1133 (SEQ ID NOs: 73, 74 and 75; and / or 90, 91 and 92); or (b) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1107 / 1108 (SEQ ID NOs: 73, 78 and 80; and / or SEQ ID NOs: 90, 91 and 95); or (c) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1150 / 1151 (SEQ ID NOs: 73, 76 and 77; and / or SEQ ID NOs: 90, 91 and 93); or (d) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 1140 / 1135 (SEQ ID NOs: 73, 78 and 79; and / or SEQ ID NOs: 90, 91 and 94); or (e) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody G12 or G12_mut or ffAC_05337 (SEQ ID NOs: 81, 82 and 83; and / or SEQ ID NOs: 96, 97, and 98); or (f) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody APX005 (SEQ ID NOs: 84, 85 and 86; and / or SEQ ID NOs: 99, 100, and 101); or (g) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody 21.4.1 (SEQ ID NOs: 87, 88 and 89; and / or SEQ ID NOs: 102, 103, and 104).

35. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises: (a) the heavy chain variable region and / or the light chain variable region of antibody 1132 / 1133 (SEQ ID NOs: 3 and 1); or (b) the heavy chain variable region and / or the light chain variable region of antibody 1107 / 1108 (SEQ ID NOs: 15 and 13); or (c) the heavy chain variable region and / or the light chain variable region of antibody 1150 / 1151 (SEQ ID NOs: 7 and 5 ); or (d) the heavy chain variable region and / or the light chain variable region of antibody 1140 / 1135 (SEQ ID NOs: 11 and 9); or (e) the heavy chain variable region and / or the light chain variable region of antibody G12 (SEQ ID NOs: 19 and 17); or (f) the heavy chain variable region and / or the light chain variable region of antibody APX005 (SEQ ID NOs: 23 and 21); or (g) the heavy chain variable region and / or the light chain variable region of antibody 21.4.1 (SEQ ID NOs: 27 and 25); or(h) the heavy chain variable region and / or the light chain variable region of antibody G12_mut (SEQ ID NOs: 29 and 17); or (i) the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NOs: 431 and 430).

36. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises the light chain of antibody 1132 / 1133 (SEQ ID NO: 372 or 379) and / or the heavy chain of antibody 1132 / 1133 (SEQ ID NO: 371 or 378).

37. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises the light chain of antibody G12 (SEQ ID NO: 381) and / or the heavy chain of antibody G12 (SEQ ID NO: 380) or the light chain of antibody G12_mut (SEQ ID NO: 383) and / or the heavy chain of antibody G12_mut (SEQ ID NO: 382).

38. The combination therapy according to any one of the preceding claims wherein binding domain B1 comprises the light chain of antibody ffAC_05337 (SEQ ID NO: 430) and / or the heavy chain of antibody ffAC_05337 (SEQ ID NO: 431).

39. The combination therapy according to any one of the preceding claims, wherein the CEA is a tumor-associated CEA.

40. The combination therapy according to any one of the preceding claims, wherein the CEA is a carcinoembryonic antigen-related cell adhesion molecule (CEACAM). 41 The combination therapy according to Claim 40, wherein the CEACAM is one or more selected from the listing consisting of: CEACAM1; CEACAM6; and CEACAM5.

42. The combination therapy according to Claim 41, wherein the CEACAM is CEACAM5.

43. The combination therapy according to any one of the preceding claims, wherein B2 which is capable of specifically binding to CEA on a target cell.

44. The combination therapy according to Claim 43, wherein the target cell is a cancer cell and / or a tumour cell.

45. The combination therapy according to Claim 44, wherein the CEA on the target cell is an intermediate level of CEA or a high level of CEA.

46. The combination therapy according to Claim 45, wherein the intermediate level of CEA is characterised by the target cell expressing about 10,000 or more CEA receptors per target cell, preferably about 50,000 or more CEA receptors per target cell.

47. The combination therapy according to Claim 45, wherein the high level of CEA is characterised by the target cell expressing about 200,000 of more CEA receptors per target cell, preferably about 300,000 of more CEA receptors per target cell.

48. The combination therapy according to any one of the preceding claims wherein binding domain B2 binds to human CEA with a KDof less than 2x10-6M or less than 1.5x10-8M or less than 2.5x10-9M or less than 2x10-9M or less than 1.5x10-12M or less than 1x10-12M, preferably less than 1.5x10-8M or less than 2.5x10-9M or less than 1.5x10-12M.

49. The combination therapy according to any one of the preceding claims wherein binding domain B2 binds preferentially to CEA on a cell over soluble CEA.

50. The combination therapy according to any one of the preceding claims, wherein binding domain B2 comprises one or more heavy chain CDR sequences selected from those in Table D(1a) and / or Table D(1b) and / or wherein binding domain B2 comprises one or more light chain CDR sequences selected from those in Table D(2).

51. The combination therapy according to any one of the preceding claims, wherein binding domain B2 comprises one, two or three light chain CDR sequences from a particular row for an individual antibody reference in Table D(2), and / or one, two or three heavy chain CDR sequences from the corresponding row for the antibody with the same reference in Table D(1a) and / or Table D(1b).

52. The combination therapy according to any one of the preceding claims wherein binding domain B2 comprises all three heavy chain CDR sequences of a particular antibody reference as shown in Table D(1a) and / or Table D(1b), and / or all three light chain CDR sequences of an antibody reference as shown in Table D(2), or wherein binding domain B1 comprises a heavy chain VH sequence and / or a light chain VL sequence as shown in Table B.

53. The combination therapy according to any one of the preceding claims, wherein B2 comprises any one, two, three, four, five or all six features independently selected from the following: (a) a heavy chain CDR1 sequence which consists of the sequence: “G, F, T, F, S, S, S, Y” or which comprises the consensus sequence of: “G, F, T, F, G / S, S, Y, Y / A”; (b) a heavy chain CDR2 sequence which consists of the sequence: “I, G, S, G, S, Y, S, T” or which comprises the consensus sequence of: “I, S, G, Y / S, G, Y / G, S, T”; (c) a heavy chain CDR3 sequence which comprises the consensus sequence of: “A, R, Y, P, S, V, P / L, F, P, Q, S, P / H / L, H / P / L, L / F / V / W, D, Y” or which comprises the consensus sequence of: “A, R, H / Y, G, Y, G / S / T, V / H, L / F, D, Y”; (d) a light chain CDR1 sequence which consists of the sequence: “Q, S, I, S, S, Y” or which comprises the consensus sequence of: “Q, S, I, R / S, S, Y”; (e) a light chain CDR2 sequence which consists of the sequence: “A, A, S”; (f) a light chain CDR3 sequence which consists of the sequence: “Q, Q, A, G, N, P, H, T” or which comprises the consensus sequence of: “Q, Q, G / Y, T / P / A, W / -, Y / -, F / V, P, F / Y, T”.

54. A combination therapy according to any one of the preceding claims wherein binding domain B2 comprises: (a) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05059 (SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218 and / or SEQ ID NOs: 90, 91 and 311) (b) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05060 (SEQ ID NOs: 219, 220 and 221 or 282, 283 and 221 and / or SEQ ID NOs: 312, 91 and 313) (c) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05061 (SEQ ID NOs: 222, 223 and 224 or 284, 285 and 224 and / or SEQ ID NOs: 90, 91 and 314) (d) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05062 (SEQ ID NOs: 222, 223 and 225 or 284, 285 and 225 and / or SEQ ID NOs: 315, 316 and 94) (e) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05064 (SEQ ID NOs: 222, 223 and 226 or 284, 285 and 226 and / or SEQ ID NOs: 90, 91 and 317) (f) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05079 (SEQ ID NOs: 216, 217 and 227 or 280, 281 and 227 and / or SEQ ID NOs: 90, 91 and 311)(g) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05080 (SEQ ID NOs: 216, 217 and 228 or 280, 281 and 228 and / or SEQ ID NOs: 90, 91 and 311) (h) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05081 (SEQ ID NOs: 216, 217 and 229 or 280, 281 and 229 and / or SEQ ID NOs: 90, 91 and 311) (i) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05082 (SEQ ID NOs: 222, 223 and 230 or 284, 285 and 230 and / or SEQ ID NOs: 90, 91 and 311) (j) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05083 (SEQ ID NOs: 222, 223 and 231 or 284, 285 and 231 and / or SEQ ID NOs: 318, 91 and 319) (k) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05084 (SEQ ID NOs: 222, 223 and 232 or 284, 285 and 232 and / or SEQ ID NOs: 90, 91 and 320) (l) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05085 (SEQ ID NOs: 219, 233 and 234 or 286, 287 and 234 and / or SEQ ID NOs: 90, 91 and 311) (m) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05086 (SEQ ID NOs: 216, 217 and 235 or 280, 281 and 235 and / or SEQ ID NOs: 90, 91 and 311) (n) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05087 (SEQ ID NOs: 216, 217 and 236 or 280, 281 and 236 and / or SEQ ID NOs: 90, 91 and 311) (o) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05088 (SEQ ID NOs: 216, 217 and 237 or 280, 281 and 237 and / or SEQ ID NOs: 90, 91 and 311) (p) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05089 (SEQ ID NOs: 216, 217 and 238 or 280, 281 and 238 and / or SEQ ID NOs: 90, 91 and 311) (q) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05090 or ffAC_05337 (SEQ ID NOs: 216, 217 and 239 or 280, 281 and 239 and / or SEQ ID NOs: 90, 91 and 311) (r) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05091 (SEQ ID NOs: 216, 217 and 240 or 280, 281 and 240 and / or SEQ ID NOs: 90, 91 and 311)(s) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05092 (SEQ ID NOs: 216, 217 and 218 or 280, 281 and 218 and / or SEQ ID NOs: 321, 91 and 311) (t) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05093 (SEQ ID NOs: 216, 217 and 241 or 280, 281 and 241 and / or SEQ ID NOs: 90, 91 and 311) (u) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05094 (SEQ ID NOs: 216, 217 and 242 or 280, 281 and 242 and / or SEQ ID NOs: 90, 91 and 311) (v) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05095 (SEQ ID NOs: 216, 217 and 243 or 280, 281 and 243 and / or SEQ ID NOs: 90, 91 and 311) (w) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05096 (SEQ ID NOs: 216, 217 and 244 or 280, 281 and 244 and / or SEQ ID NOs: 90, 91 and 311) (x) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05097 (SEQ ID NOs: 217, 216 and 245 or 280, 281 and 245 and / or SEQ ID NOs: 90, 91 and 311) (y) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05098 (SEQ ID NOs: 219, 220 and 246 or 282, 283 and 246 and / or SEQ ID NOs: 312, 91 and 313) (z) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05099 (SEQ ID NOs: 222, 223 and 224 or 288, 285 and 224 and / or SEQ ID NOs: 90, 91 and 311) (aa) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody AC_05100 (SEQ ID NOs: 222, 223 and 247 or 288, 285 and 247 and / or SEQ ID NOs: 90, 91 and 311) (ab) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab1 (SEQ ID NOs: 248, 249 and 250 or 289, 290 and 250 and / or SEQ ID NOs: 90, 91 and 322) (ac) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab2 (SEQ ID NOs: 251, 252 and 253 or 291, 292 and 253 and / or SEQ ID NOs: 90, 91 and 323) (ad) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab3 (SEQ ID NOs: 254, 255 and 256 or 293, 294 and 256 and / or SEQ ID NOs: 324, 325 and 326)(ae) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab4 (SEQ ID NOs: 257, 258 and 259 or 295, 296 and 259 and / or SEQ ID NOs: 90, 91 and 327) (af) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab5 (SEQ ID NOs: 260, 261 and 262 or 297, 298 and 262 and / or SEQ ID NOs: 324, 325 and 328) (ag) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab6 (SEQ ID NOs: 263, 264 and 265 or 299, 300 and 265 and / or SEQ ID NOs: 324, 325 and 329) (ah) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab7 (SEQ ID NOs: 266, 267 and 268 or 301, 302 and 268 and / or SEQ ID NOs: 90, 91 and 330) (ai) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab8 (SEQ ID NOs: 269, 270 and 271 or 303, 304 and 271 and / or SEQ ID NOs: 90, 91 and 331) (aj) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab9 (SEQ ID NOs: 272, 335 and 273 or 305, 306 and 273 and / or SEQ ID NOs: 90, 91 and 332) (ak) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab10 (SEQ ID NOs: 274, 275 and 276 or 307, 308 and 276 and / or SEQ ID NOs: 90, 91 and 333) and / or (al) the three CDRs of the heavy chain and / or the three CDRs of the light chain of antibody Fab11 (SEQ ID NOs: 277, 278 and 279 or 309, 310 and 279 and / or SEQ ID NOs: 324, 325 and 334).

55. The combination therapy according to any one of the preceding claims wherein binding domain B2 comprises: (a) the heavy chain variable region and / or the light chain variable regionantibody AC_05059 (SEQ ID NO: 33 and / or SEQ ID NO: 31) (b) the heavy chain variable region and / or the light chain variable region of antibody AC_05060 (SEQ ID NO: 37 and / or SEQ ID NO: 35) (c) the heavy chain variable region and / or the light chain variable region of antibody AC_05061 (SEQ ID NO: 41 and / or SEQ ID NO: 39) (d) the heavy chain variable region and / or the light chain variable regionantibody AC_05062 (SEQ ID NO: 45 and / or SEQ ID NO: 43) (e) the heavy chain variable region and / or the light chain variable region of antibody AC_05064 (SEQ ID NO: 49 and / or SEQ ID NO: 47)(f) the heavy chain variable region and / or the light chain variable region of antibody AC_05079 (SEQ ID NO: 53 and / or SEQ ID NO: 51) (g) the heavy chain variable region and / or the light chain variable region of antibody AC_05080 (SEQ ID NO: 57 and / or SEQ ID NO: 55) (h) the heavy chain variable region and / or the light chain variable region of antibody AC_05081 (SEQ ID NO: 61 and / or SEQ ID NO: 59) (i) the heavy chain variable region and / or the light chain variable region of antibody AC_05082 (SEQ ID NO: 65 and / or SEQ ID NO: 63) (j) the heavy chain variable region and / or the light chain variable region of antibody AC_05083 (SEQ ID NO: 69 and / or SEQ ID NO: 67) (k) the heavy chain variable region and / or the light chain variable region of antibody AC_05084 (SEQ ID NO: 106 and / or SEQ ID NO: 71) (l) the heavy chain variable region and / or the light chain variable region of antibody AC_05085 (SEQ ID NO: 110 and / or SEQ ID NO: 108) (m) the heavy chain variable region and / or the light chain variable region of antibody AC_05086 (SEQ ID NO: 114 and / or SEQ ID NO: 112) (n) the heavy chain variable region and / or the light chain variable region of antibody AC_05087 (SEQ ID NO: 118 and / or SEQ ID NO: 116) (o) the heavy chain variable region and / or the light chain variable region of antibody AC_05088 (SEQ ID NO: 122 and / or SEQ ID NO: 120) (p) the heavy chain variable region and / or the light chain variable region of antibody AC_05089 (SEQ ID NO: 126 and / or SEQ ID NO: 124) (q) the heavy chain variable region and / or the light chain variable region of antibody AC_05090 (SEQ ID NO: 130 and / or SEQ ID NO: 128) (r) the heavy chain variable region and / or the light chain variable region of antibody AC_05091 (SEQ ID NO: 134 and / or SEQ ID NO: 132) (s) the heavy chain variable region and / or the light chain variable region of antibody AC_05092 (SEQ ID NO: 138 and / or SEQ ID NO: 136) (t) the heavy chain variable region and / or the light chain variable region of antibody AC_05093 (SEQ ID NO: 142 and / or SEQ ID NO: 140) (u) the heavy chain variable region and / or the light chain variable region of antibody AC_05094 (SEQ ID NO: 146 and / or SEQ ID NO: 144) (v) the heavy chain variable region and / or the light chain variable region of antibody AC_05095 (SEQ ID NO: 150 and / or SEQ ID NO: 148) (w) the heavy chain variable region and / or the light chain variable region of antibody AC_05096 (SEQ ID NO: 154 and / or SEQ ID NO: 152) (x) the heavy chain variable region and / or the light chain variable region of antibody AC_05097 (SEQ ID NO: 158 and / or SEQ ID NO: 156)(y) the heavy chain variable region and / or the light chain variable region of antibody AC_05098 (SEQ ID NO: 162 and / or SEQ ID NO: 160) (z) the heavy chain variable region and / or the light chain variable region of antibody AC_05099 (SEQ ID NO: 166 and / or SEQ ID NO: 164) (aa) the heavy chain variable region and / or the light chain variable region of antibody AC_05100 (SEQ ID NO: 170 and / or SEQ ID NO: 168) (ab) the heavy chain variable region and / or the light chain variable region of antibody Fab1 (SEQ ID NO: 174 and / or SEQ ID NO: 172) (ac) the heavy chain variable region and / or the light chain variable region of antibody Fab2 (SEQ ID NO: 178 and / or SEQ ID NO: 176) (ad) the heavy chain variable region and / or the light chain variable region of antibody Fab3 (SEQ ID NO: 182 and / or SEQ ID NO: 180) (ae) the heavy chain variable region and / or the light chain variable region of antibody Fab4 (SEQ ID NO: 186 and / or SEQ ID NO: 184) (af) the heavy chain variable region and / or the light chain variable region of antibody Fab5 (SEQ ID NO: 190 and / or SEQ ID NO: 188) (ag) the heavy chain variable region and / or the light chain variable region of antibody Fab6 (SEQ ID NO: 194 and / or SEQ ID NO: 192) (ah) the heavy chain variable region and / or the light chain variable region of antibody Fab7 (SEQ ID NO: 198 and / or SEQ ID NO: 196) (ai) the heavy chain variable region and / or the light chain variable region of antibody Fab8 (SEQ ID NO: 202 and / or SEQ ID NO: 200) (aj) the heavy chain variable region and / or the light chain variable region of antibody Fab9 (SEQ ID NO: 206 and / or SEQ ID NO: 204) (ak) the heavy chain variable region and / or the light chain variable region of antibody Fab10 (SEQ ID NO: 210 and / or SEQ ID NO: 208) (al) the heavy chain variable region and / or the light chain variable region of antibody Fab11 (SEQ ID NO: 214 and / or SEQ ID NO: 212) (am) the heavy chain variable region and / or the light chain variable region of antibody mAb2 (SEQ ID NO: 387 and / or SEQ ID NO: 385) and / or (an) the heavy chain variable region and / or the light chain variable region of antibody ffAC_05337 (SEQ ID NO: 433 and / or SEQ ID NO: 432).

56. The combination therapy according to any one of the preceding claims wherein binding domain B2 comprises: (a) the light chain and / or the heavy chain of antibody AC_05059 (SEQ ID NO: 388 and / or SEQ ID NO: 389)(b) the light chain and / or the heavy chain of antibody AC_05060 (SEQ ID NO: 390 and / or SEQ ID NO: 391) (c) the light chain and / or the heavy chain of antibody AC_05061 (SEQ ID NO: 392 and / or (SEQ ID NO: 393) (d) the light chain and / or the heavy chain of antibody AC_05062 (SEQ ID NO: 394 and / or SEQ ID NO: 395) (e) the light chain and / or the heavy chain of antibody AC_05064 (SEQ ID NO: 396 and / or SEQ ID NO: 397) (f) the light chain and / or the heavy chain of antibody AC_05079 (SEQ ID NO: 398 and / or SEQ ID NO: 399) (g) the light chain and / or the heavy chain of antibody AC_05081 (SEQ ID NO: 400 and / or SEQ ID NO: 401) (h) the light chain and / or the heavy chain of antibody AC_05088 (SEQ ID NO: 402 and / or SEQ ID NO: 403) (i) the light chain and / or the heavy chain of antibody AC_05089 (SEQ ID NO: 404 and / or SEQ ID NO: 405) (j) the light chain and / or the heavy chain of antibody AC_05090 (SEQ ID NO: 406 and / or SEQ ID NO: 407) (k) the light chain and / or the heavy chain of antibody AC_05091 (SEQ ID NO: 408 and / or SEQ ID NO: 409) (l) the light chain and / or the heavy chain of antibody AC_05093 (SEQ ID NO: 410 and / or SEQ ID NO: 411) (m) the light chain and / or the heavy chain of antibody AC_05094 (SEQ ID NO: 412 and / or SEQ ID NO: 413) (n) the light chain and / or the heavy chain of antibody AC_05096 (SEQ ID NO: 414 and / or SEQ ID NO: 415) (o) the light chain and / or the heavy chain of antibody AC_05097 (SEQ ID NO: 416 and / or SEQ ID NO: 417) (p) the light chain and / or the heavy chain of antibody Fab1 (SEQ ID NO: 418 and / or SEQ ID NO: 419) (q) the light chain and / or the heavy chain of antibody Fab3 (SEQ ID NO: 420 and / or (SEQ ID NO: 421).

57. The combination therapy according to any one of the preceding claims wherein the bispecific polypeptide: x comprises a Chain H1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 359; SEQ ID NO: 362; SEQ ID NO: 365; and / or SEQ ID NO: 367; and / orx comprises a Chain L1 comprising a sequence selected from the listing consisting of: SEQ ID NO: 360; SEQ ID NO: 363; SEQ ID NO: 372; and / or SEQ ID NO: 368; and / or x comprises a Chain H2 comprising a sequence selected from the listing consisting of: SEQ ID NO: 361; SEQ ID NO: 364; SEQ ID NO: 366; and / or SEQ ID NO:

369.

58. A combination therapy according to any one of the preceding claims wherein said PD-1 inhibitor comprises or consists of an anti-PD-1 antibody, or antigen-binding fragment thereof capable of inhibiting PD-1 function.

59. A combination therapy according to Claim 58 wherein the anti-PD-1 antibody is selected from the group consisting of Nivolumab, Pembrolizumab, Pidilizumab, Cemiplimab, AMP-224, PDR-001, MEDI-0680, JTX-4014 (Pimivalimab), Spartalizumab, Camrelizumab, Sintilimab, Tislelizumab, Toripalimab, Dostarlimab, INCMGA00012 (Retifanlimab) and Acrixolimab, preferably wherein the anti-PD-1 antibody is Nivolumab.

60. A combination therapy according to any one of the preceding claims wherein said PD-1 inhibitor comprises or consists of an anti-PD-L1 antibody, or antigen-binding fragment thereof capable of inhibiting PD-1 function.

61. A combination therapy according to Claim 60 wherein the anti-PD-L1 antibody is selected from the group consisting of Atezolizumab (MPDL3280A), Durvalumab (MEDI 4736), Avelumab, MDX-1105, KN035 (Envafolimab) and CK-301 (Cosibelimab).

62. A combination therapy according to Claims 1-59, wherein: (a) binding domain B1 comprises three heavy chain CDRs of SEQ ID NOs: 81, 82 and 83 and three light chain CDRs of SEQ ID NOs: 96, 97, and 98; (b) binding domain B2 comprises three heavy chain CDRs of SEQ ID NOs 216, 217 and 239 and three light chain CDRs of SEQ ID NOs: 90, 91, and 311; and (c) the PD-1 inhibitor is Nivolumab.

63. A pharmaceutical composition comprising an effective amount of: (a) a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain,designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) a PD-1 inhibitor, wherein the PD-1 inhibitor is formulated for parenteral delivery.

64. The pharmaceutical composition according to Claim 63, wherein the parenteral delivery is intravenous administration, subcutaneous administration or intratumoural administration.

65. The pharmaceutical composition according to Claim 63 or 64 wherein the bispecific polypeptide is as defined in any one of Claims 1 to 57 or 62.

66. The pharmaceutical composition according to any one of Claims 63 to 65 wherein the PD-1 inhibitor is as defined in any one of Claims 58 to 62.

67. The pharmaceutical composition according to any one of Claims 63 to 66 wherein: (a) binding domain B1 comprises three heavy chain CDRs of SEQ ID NOs: 81, 82 and 83 and three light chain CDRs of SEQ ID NOs: 96, 97, and 98; (b) binding domain B2 comprises three heavy chain CDRs of SEQ ID NOs 216, 217 and 239 and three light chain CDRs of SEQ ID NOs: 90, 91, and 311; and (c) the PD-1 inhibitor is Nivolumab.

68. A combination therapy according to any one of Claims 1 to 62 or a pharmaceutical composition according to any one of Claims 63 to 67 wherein the daily dosage level of the PD-1 inhibitor is: (d) from 1 mg / kg bodyweight of a subject to 100 mg / kg body weight of a subject; (e) From 1 mg / kg bodyweight of a subject to 20 mg / kg body weight of a subject; or (f) Is 1 mg / kg, 10 mg / kg, 20 mg / kg, 100 mg / kg bodyweight of a subject, preferably 10 mg / kg bodyweight.

69. A combination therapy according to any one of Claims 1 to 62 or 68, or a pharmaceutical composition according to any one of Claims 63 to 68 wherein the concentration of PD-1 inhibitor is between approximately 2 mg / ml and 150 mg / ml or between approximately 2 mg / ml and 200 mg / ml, preferably wherein the concentration of PD-1 inhibitor is from 10 mg / ml to 25 mg / ml.

70. A combination therapy according to any one of Claims 1 to 62, 68 or 69 or a pharmaceutical composition according to any one of Claims 63 to 69 wherein the dose of the PD-1 inhibitor is from between 10 mg to 1500 mg, optionally wherein the dose is from 100 mg to 200 mg, or from 200 mg to 500 mg.

71. A combination therapy according to any one of Claims 1 to 62 or 68 to 70, or a pharmaceutical composition according to any one of Claims 63 to 70, wherein: (a) the PD-1 inhibitor is pembrolizumab used at a dose of approximately 25 mg / ml, 200mg (intravenous) every 3 weeks or 400 mg (intraveneously) every 6 weeks; (b) the PD-1 inhibitor is nivolumab used at a dose of approximately 10 mg / ml, 250 mg (intravenous) every 2 weeks or 480 mg (intravenous) every 4 weeks; or (c) the PD-1 inhibitor is atezolizumab used a dose of approximately 60mg / ml. 840 mg (intravenous) every 2 weeks or 1200 mg (intravenous) every 4 weeks.

72. The combination therapy according to any one of Claims 1 to 62 or 68 to 71, or the pharmaceutical composition according to any one of Claims 63 to 71 for use in medicine.

73. Use of a combination therapy according to any one of Claims 1 to 62 or 68 to 71 or the pharmaceutical composition according to any one of Claims 63 to 71, in the preparation of a medicament.

74. A method for the treatment of a cancer and / or a tumour in a subject, comprising (a) administering to the subject an effective amount of a bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA), and (b) administering to the subject an effective amount of a PD-1 inhibitor, wherein the PD-1 inhibitor is administered parenterally.

75. A method according to Claim 74 wherein the bispecific polypeptide is as defined in any one of Claims 1 to 57 or 62.

76. A method according to Claim 74 or 75 wherein the PD-1 inhibitor is as defined in any one of Claims 58 to 62.

77. A combination therapy or pharmaceutical composition according to Claim 72 or a method according to any one of Claims 74 to 76 wherein the bispecific polypeptide and the PD-1 inhibitor are administered simultaneously or within 24 hours of each other.

78. A combination therapy or pharmaceutical composition according to Claim 72 or 77 or a method according to any one of Claims 74 to 77 wherein the bispecific polypeptide and / or the PD-1 inhibitor are administered parenterally.

79. A combination therapy, pharmaceutical composition or method according to Claim 78 wherein the administration is intravenous, subcutaneous or intratumoural.

80. A combination therapy or pharmaceutical composition according to Claim 72, 77-79 or a method according to any one of Claims 74 to 69 wherein the dose of PD-1 inhibitor is: (j) between approximately 1 and 100 mg / kg bodyweight of the patient, optionally wherein the dose of the PD-1 inhibitor is 1 mg / kg, 10 mg / kg, 20 mg / kg or 100 mg / kg; and / or (iii) between approximately 2 mg / ml and 200 mg / ml, optionally wherein the dose is 2mg / ml, 10 mg / ml, 25 mg / ml, 150 mg / ml or 200 mg / ml; optionally wherein the PD-1 inhibitor is administered in a single or divided doses.

81. A bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA) for use in medicine, wherein the bispecific polypeptide is for use in combination with a PD-1 inhibitor and wherein the PD-1 inhibitor is formulated for parenteral administration.

82. A bispecific polypeptide comprising a first binding domain, designated B1, which is capable of binding specifically to CD40, and a second binding domain, designated B2, which is capable of specifically binding to carcinoembryonic antigen (CEA) for use in the treatment of a cancer and / or a tumour in a subject, wherein the bispecific polypeptide is for use in combination with a PD-1 inhibitor and wherein the PD-1 inhibitor is formulated for parenteral administration.

83. The bispecific polypeptide for use according to Claim 81 or 82, wherein the bispecific polypeptide is as defined in any one of Claims 1 to 57 or 62.

84. The bispecific polypeptide for use according to Claim 81 to 83, wherein the PD-1 inhibitor is as defined in any one of Claims 63 to 71.

85. The method according to any one of Claims 74 to 80 or the bispecific polypeptide for use according to any one of Claims 82 to 84, wherein the tumour is a solid tumour.

86. The combination therapy according to Claim 68-72, or the method according to any one of Claims 74 to 85, wherein the subject is human.

87. A combination therapy, pharmaceutical composition, bispecific polypeptide, method or use substantially as described herein with reference to the description and figures.

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