21 results about "CAR T-cell therapy" patented technology

Provided are polypeptides that include, from N-terminus to C-terminus, a chimeric antigen receptor (CAR), a protease, and a degron, where the polypeptide further includes a cleavage site for the protease disposed between the CAR and the degron. Also provided are cells that include such polypeptides (e.g., where the cells express the CAR on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the polypeptides, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for controlling the expression of a CAR on the surface of a cell, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable CAR cell-based therapy (e.g., a regulatable CAR T cell therapy) to an individual.

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and / or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3ζ segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FRα) and a segment that that can specifically bind to a human CD3□ segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.

The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising chimeric antigen receptors (CARs) specific for CD45. In certain embodiments, the modified immune cells or precursors thereof further comprise or instead comprise a modified endogenous gene locus encoding CD45.

A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.

The invention provides a drug combination composition for in-vivo target cell engineering modification, and target cells do not include myeloid cells. The drug combination composition comprises a first drug and a second drug, wherein the active ingredient of the first drug is a substance capable of saturating, inhibiting or eliminating phagocytic ability of in-vivo myeloid cells, and the active ingredient of the second drug is an in-vivo target cell capable of being engineered. Through combined application of the myeloid cell inhibition drug and the cell engineering modification drug targeting the target cells, endocytosis of the myeloid cells to the target drug is reduced or eliminated before engineering modification of the target cells, so that the off-target effect is reduced, the lymphatic organ targeting property can be improved, and the treatment effect of the myeloid cells is improved. The toxic and side effects of cell engineering modification drugs on the liver are reduced, and the method has important significance on in-vivo (in-situ) lymphocyte engineering modification (including gene editing) or immunotherapy (such as in-vivo CAR T cell therapy).

This document relates to methods and materials involved in treating cancer. For example, methods and materials for using chimeric antigen receptor (CAR) T cells having reduced levels of an interleukin (IL) 4 polypeptide, having reduced levels of a transcription factor 7 (TCF7) polypeptide, having reduced levels of a protein tyrosine phosphatase non-receptor type 2 (PTPN2) polypeptide, and / or having reduced levels of a protein tyrosine phosphatase non-receptor type 3 (PTPN3) polypeptide are provided. Methods and materials for using such CAR T cells in an adoptive cell therapy (e.g., a CAR T cell therapy) to treat a mammal (e.g., a human) having cancer also are provided

The present application provides a method for batch preparation of immune cell therapy products without electric conversion, the CD7 gene of the immune cells is knocked out and a chimeric antigen receptor targeting CD7 is expressed at the same time, the method comprises producing engineered viroplasm by a stable cell line, knocking out the CD7 gene in the immune cells by using the engineered viroplasm, and transducing the immune cells by using a CD7 CAR retrovirus vector, thereby obtaining the immune cell therapy product. The present application aims at the difficulties in the current CAR-T cell preparation, such as high cost, poor popularity, and high risk of failure in the application of CRISPR electric conversion technology, introduces eVLP technology for efficient and convenient gene editing, and ensures safety, saves cost, reduces operation complexity, and greatly improves the success rate of immune cell preparation. Based on clinical needs, the present application uses a CD7 eVLP vector combined with a CD7 CAR retrovirus to construct a CD7 KO+CD7 CAR T cell therapy product.

The present disclosure provides a method of treating autoimmune diseases such as multiple sclerosis, comprising the use of anti-CD20 chimeric antigen receptor (CAR) that contains a hybrid single chain variable fragment (scFv), wherein the framework regions (FRs) and complementarity-determining regions (CDRs) of the scFv are derived from different anti-CD20 antigen binding regions or anti-CD20 antibodies. Furthermore, the CAR comprises a torsional linker (e.g. 1-4 alanine residues) between the transmembrane domain and the cytoplasmic region of the CAR.

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and / or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.

The application provides use of a TRIM21 inhibitor in preparation of a product for enhancing tumor immunity effect. Specifically, the application provides use of a TRIM21 inhibitor in preparation of a product for inhibiting TRIM21 from improving application of an immune checkpoint CTLA-4 therapeutic antibody and CAR T cell therapy in tumor treatment. + The application finds that, in a mouse tumor model, whole-body knockout of Trim21 significantly reduces expression amount of an immune checkpoint PD-1 protein and activates cytotoxic CD8 T lymphocytes, thereby enhancing sensitivity of the tumor to the CTLA-4 therapeutic antibody. Moreover, the CAR T cell with the knockout of Trim21 has stronger anti-tumor capacity.

The present invention provides improved anti-BCMA CAR T cell compositions and methods for producing anti-BCMA CAR T cell therapies. More specifically, the present invention relates to improved methods for producing anti-BCMA CAR T cells that produce stronger, longer-lasting, and more effective adoptive T cell immunotherapy. In certain embodiments, the cells are produced from subjects with multiple myeloma or lymphoma.

Provided herein are improved methods for robust TCR+ cell depletion and production of populations of TCR− cells, which can be beneficial to minimize the GvHD risk in patients receiving allogeneic CAR T cell therapy. Provided herein are methods that increase the efficiency of depleting TCR+ cells from a population of cells in order to significantly reduce any residual levels of TCR+ cells present in cell populations in which expression of endogenous TCR has been reduced or eliminated. Associated kits and cell populations are also provided.

This disclosure provides a system for preventing or reducing side effects in a patent undergoing immunotherapy to remove diseased cells that express a target antigen: for example, by CAR T cell therapy. Side effects can ensue from concurrent depletion of hematopoietic cells bearing the same target antigen. A population of engineered hematopoietic cells is prepared by obtaining healthy hematopoietic cells from the patient or a third party donor, and using them to produce engineered hematopoietic cells. The engineered cells either do not express the target antigen, express it at a lower density, or express it in a modified form. The engineered hematopoietic cells are formulated for administration to the patient, whereupon they reconstitute hematopoietic cell function, thereby preventing or reducing the side effects.

This document provides methods and materials involved in treating cancer. For example, methods and materials for generating immune cells (e.g., T cells) that (1) can constitutively express one or more chimeric antigen receptors (CARs) having the ability to bind a cancer-specific antigen and (2) can express an agent that can target a cell of a tumor microenvironment (TME) when the CAR is activated (e.g., by binding to a cancer cell expressing that cancer-specific antigen) are provided. Also provided are methods and materials for using such CAR T cells in an adoptive cell therapy (e.g., a CAR T cell therapy) to treat a mammal (e.g., a human) having cancer.

The present disclosure relates to CD19 CAR-T cell products and methods of treating recurrent or refractory CD19 + hematological malignancies.

This document provides methods and materials for treating a mammal having cancer. For example, T cells (e.g., chimeric antigen receptor (CAR) T cells) engineered to express an antigen receptor (e.g., a CAR) that can target a thyroid stimulating hormone receptor (TSHR) polypeptide are provided. In some cases, T cells provided herein can be administered to a mammal having cancer to treat the mammal. For example, one or more T cells expressing (e.g., engineered to express) an antigen receptor (e.g., a CAR) that can target a TSHR polypeptide can be administered (e.g., in an adoptive cell therapy such as a CAR T cell therapy) to a mammal (e.g., a human) having cancer (e.g., thyroid cancer) to treat the mammal.

Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON / OFF switch (with the ability for tenability / titrability), (b) sense multiple antigens and perform logic computations, and / or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and / or cells in the treatment of cancer.

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3ζ segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FRα) and a segment that that can specifically bind to a human CD3ε segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.