148 results about "Adoptive cellular therapy" patented technology

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

Provided herein are chimeric receptors, including chimeric antigen receptors (CARs), comprising BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof, including heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, including a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof including in adoptive cell therapy.

Disclosed are VHH chimeric antigen receptors (VCARs), VCAR transposons encoding VCARs of the disclosure, cells modified to express VCARs of the disclosure, as well as methods of making and methods of using the same for adoptive cell therapy.

The present disclosure relates generally to compositions and methods for improving T cell therapy. In particular, the disclosure provides polypeptides and recombinant nucleic acid constructs and / or recombinant nucleic acids encoding polypeptides having mutations capable of effecting altering T cell signaling, cytokine production, and / or in vivo persistence of therapeutic T cells comprising the mutations in tumors. The T cell signaling may be carried out by the NFAT, NF-[kappa] B, and / or AP-1 pathway. The disclosure also provides vectors and cells comprising the polypeptides and / or recombinant nucleic acid constructs and / or recombinant nucleic acids of the disclosure, as well as methods of making T cells for use in cell therapy, and methods of identifying mutations useful for improving T cell therapy.

The present disclosure relates to T cells capable of co-expressing T cell receptors (“TCR”) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and / or NK cells. The methods can include inhibitory RNA molecule(s) and / or engineered signaling polypeptides that can include a lymphoproliferative element, and / or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and / or genetically modified T cells and / or NK cells are provided, such as, for example, those including riboswitches, MRB-CARS, recognition domains, and / or pH-modulating agents.

The present invention relates to compositions and methods for the treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor. One aspect includes a modified canine T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity in canine.

Provided herein are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain plasma cell malignancy. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for treating subjects with multiple myeloma (MM). Also provided are genetically engineered cells containing such BCMA-binding receptors for uses in adoptive cell therapy.

The invention relates to the field of radiotherapy and, more particularly, to the use of a compound based on FMS-like tyrosine kinase 3 ligand (FLT3L) and adoptive cell therapy using dendritic cells in the prevention of cognitive damage associated with radiotherapy.

The invention belongs to the technical field of tumor immunity, and particularly relates to a tumor antigen and chemotactic factor co-coding system and application thereof. The invention provides a tumor antigen and chemotactic factor co-coding system. The tumor antigen and chemotactic factor co-coding system comprises a nucleotide sequence for coding a tumor antigen and a nucleotide sequence for coding a chemotactic factor. The tumor antigen and chemotactic factor co-coding system can flexibly replace an antigen sequence and chemotactic factor combination, is adaptive to different tumor types and various immunotherapy requirements, can be expanded to various solid tumor treatment scenes through a customized antigen-chemotactic factor combination in the future, and has a wide application prospect. The broad-spectrum application in tumor treatment means including tumor neoantigen vaccines, adoptive cell therapy and the like is realized.

Methods are provided for generating unlimited immune cells with increased lifespan and high proliferation rate by modifying them to express BCL6 and genes that promote cell survival. Further methods are provided for generating and using said unlimited immune cells to treat diseases such as cancer.

The invention discloses an application of Tapinarof in improvement of a tumor treatment effect. According to the application, a compound Tapinarof is found through screening, experimental research finds that the Tapinarof has an anti-tumor effect, and the Tapinarof can enhance the anti-tumor function of T cells, so that the curative effects of an immune checkpoint inhibitor and adoptive T cell therapy are improved, and the Tapinarof and the immune checkpoint inhibitor / adoptive cell transfer therapeutic agent have a synergistic effect in combined treatment of tumors. The discovery supports the potential value of the Tapinarof as an adjuvant therapy drug in clinical application of cancer immunotherapy.

The present invention relates to a lymphocyte comprising a recombinant nucleic acid encoding a fusion protein comprising interleukin-15 (IL-15) fused to interleukin-21 (IL-21), and optionally further comprising a recombinant antigen receptor and further optionally rendered independent of CD28 co-stimulation and resistant to exhaustion as caused by checkpoint protein expression and activation. The invention further encompasses the use of such lymphocytes, particularly in therapeutic applications such as adoptive cell therapy for cancer, autoimmune diseases, or infectious diseases. Also included within the scope of the invention are fusion proteins comprising IL-15 and IL-21 domains, nucleic acids encoding such fusion proteins, and cells—such as lymphocytes or other suitable host cells—comprising these nucleic acids.

A nucleic acid sequence comprising: (i) a nucleotide sequence S1 encoding a CD8α polypeptide, (ii) a nucleotide sequence S2 encoding a CD8β polypeptide, (iii) a nucleotide sequence S3 encoding a T-cell receptor (TCR) α polypeptide, and (iv) a nucleotide sequence S4 encoding a TCRβ polypeptide, wherein the nucleotide sequences are arranged in tandem in a 5'-to-3' orientation S2-S1-S4-S3, wherein the CD8α polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 11, and the CD8β polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 12.

Compositions, systems, and kits are disclosed that comprise at least one immune checkpoint inhibitor and at least one immune cell type for adoptive cell therapy, wherein the at least one immune cell type has been fucosylated ex vivo (fuco-ACT). Also disclosed are methods of making and using the compositions, systems, and kits.

Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered monocytes or engineered monocyte-derived macrophages that overexpress ID3 for the treatment of cancer.

Disclosed herein is a method for ex vivo expanding tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). The method involves culturing tumor fragments from the subject in a culture medium containing IL-2 and a 41BB agonist in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity. Also disclosed is a method for treating a tumor in a subject that involves treating the subject with nonmyeloablative lymphodepleting chemotherapy, and administering tumor-infiltrating lymphocytes expanded by the disclosed methods.

The present technology relates to methods, computing devices, and systems for predicting the fitness of mutant p53 based on the loss of transcription factor function and immunogenicity of a particular TP53 mutation. The fitness of mutant p53 may be used to determine whether a patient will benefit from a particular anti-cancer therapy such as immune checkpoint inhibitor therapy, adoptive T-cell therapy, or prophylactic cancer vaccine therapy.

Disclosed are composition comprising (a) an inducible transgene construct, comprising a sequence encoding an inducible promoter and a sequence encoding a transgene, and (b) a receptor construct, comprising a sequence encoding a constitutive promoter and a sequence encoding an exogenous receptor, wherein, upon integration of the construct of (a) and the construct of (b) into a genomic sequence of a cell, the exogenous reporter is expressed, and wherein the exogenous reporter, upon binding a ligand, transduces an intracellular signal that targets the inducible promoter of (a) to modify gene expression. Methods for introducing compositions into cells and the use of the resultant cells in adoptive cell therapies are also provided.

Delta-like ligand 3 (DLL3) binding molecules, particularly human antibodies, including antibody fragments, specific for DLL3 are provided. Also provided are recombinant receptors, including chimeric antigen receptors (CARs) comprising such antibodies or fragments, and polynucleotides encoding antibodies, antigen binding fragments or receptors specific for DLL3. Also provided are genetically engineered cells containing such DLL3 binding proteins and receptors, as well as related methods and uses thereof in adoptive cell therapy.

The invention relates to the fields of life science and medicine. In particular, the present invention relates to cancer therapy in humans. More specifically, the present invention relates to oncolytic adenoviral vectors encoding bispecific monoclonal antibodies. In addition, the present invention relates to methods and uses utilizing oncolytic adenoviral vectors and along with adoptive cell therapy.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

Embodiments of the disclosure concern methods and compositions related to T cell receptors directed against breast cancer neoantigens, including immunotherapeutic compositions of any kind. In specific embodiments, the TCRs are identified following particular methods of producing neoantigen-specific T cells, including particular culturing methods.

The invention provides improved compositions and methods for the treatment of solid cancers.

The application relates to modified immune effector cells with enhanced immune cell function, as well as related pharmaceutical compositions. The application further relates to methods for generating the modified immune effector cell and methods for using the modified immune effector cell for treatment of diseases (e g., adoptive cell therapy).

Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered immune cells that overexpress miR200c and / or EpCAM.

Methods for screening neoantigen peptides, to identify those that induce T lymphocyte ("T cell") expansion, generating functional T cell compositions comprising T cells specific for one or more neoantigen epitopes and treating cancer by adoptive cell therapy are provided.

Provided herein are methods for the production of tissue resident memory-like T cells by the combination of hypoxia and TGFβ. Further provided herein are methods of using the tissue resident memory T cells as adoptive cell therapy.