Provided herein are modified T lymphocytes comprising chimeric receptors and methods of use thereof.

The present invention provides compositions and methods for inducing tolerance in a human. The invention includes administering a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

The present invention provides compositions and methods for regulating the specificity and activity of immune effector cells for use in immunotherapy. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a NKR-CAR which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Anti-ADAM12 agents are provided such as anti-ADAM12 antibodies (Abs), antigen-binding Ab fragments, multi-specific Abs and antigen-binding Ab fragments, antibody-drug conjugates (ADCs), and chimeric antigen receptors (CARs). Also, nucleic acid sequences and vectors are provided encoding, cells and pharmaceutical compositions comprising such anti-ADAM12 agents and methods for expanding such cells. Methods of treating, preventing, or diagnosing a disease such as cancer and methods of stimulating an immune response using such materials are also provided.

CAR cells and humanized antibodies targeting DCLK1 expressed on/in tumor cells or circulating cancer cells are described as a new method of cancer treatment. The antibodies and cells are safe and effective in patients and can be used to treat cancer expressing the DCLK1 proteins.

The present invention provides methods of use for compositions comprising an immunotherapeutic such as chimeric antigen receptor T cells (CAR-T cells), and specifically those that target a tumor antigen cleaved by gamma secretase, in combination with bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof;

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for treating lymphomas.

The present invention relates to humanized HER2 single domain antibodies and variants thereof and their use in therapy and for cancer diagnosis. The invention most particularly proposes chimeric antigen receptors including said humanized HER2 sdAb in their antigen binding domain and their use in cancer cell therapy.

A novel chimeric receptor composition, a recombinant vector, a cell, and an application thereof. The novel chimeric receptor composition includes a conventional chimeric antigen receptor (CAR), and a NKG2D chimeric receptor including a full-length sequence or a truncated fragment of NKG2D, DAP10, and/or DAP12, referred to as a SNR-armed CAR. The chimeric receptor composition enables a conventional CAR-T cell to express a NKG2D extracellular domain and an intracellular signal domain, expands a CAR-T antigen recognition spectrum, solves the tumor heterogeneity, achieves a lower level of cytokine release while enhancing the killing capability of CAR-T on tumor cells expressing target antigens, reduces the possibility of cytokine storm occurrence, and improves the CAR-T security.

The present disclosure relates to T cells engineered to comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG, a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA, and insertion of sequence(s) encoding a regulatory T cell promoting molecule and compositions and uses thereof.

Provided herein are vectors comprising a polycistronic expression casstte comprising a polynucleotide that encodes a CD 19 specific chimeric antigen receptor, a polynucleotide that encodes a cytokine, and a polynucleotide that encodes a marker protein, wherein the polynucleotide that encodes the CD 19-specific chimeric antigen receptor and the polynucleotide that encodes the cytokine coding sequence are separated by a polynucleotide sequence that comprises an F2A element, and wherein the polynucleotide sequence that encodes the cytokine and the polynucleotide sequence that encodes the marker protein are separated by a polynucleotide sequence that comprises a T2A element.