Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b)a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with ?-secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with ?-secretase inhibitor can be used in, for example, adoptive immunotherapy.

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.

Disclosed are compositions and methods for targeted treatment of cancer. The present disclosure provides chimeric antigen receptors and cells expressing such chimeric antigen receptors. In certain embodiments, engineered cells expressing the chimeric antigen receptors are specific for a low density cancer antigen or peptide in groove antigen.

Disclosed herein are compositions and methods for a cell culture system for differentiating stem cells into, e.g., engraftable hematopoietic progenitor cells (HPCs), myeloid and/or lymphoid hematopoietic cells. In particular, the invention relates to producing hemogenic clusters of cells from pluripotent stem cells (e.g., embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)), culturing the clusters of cells to form a vascular organoid, and derivation of HPCs, natural killer (NK) cells, or myeloid cells using the vascular organoid. The present disclosure further relates to methods of modifying various stem cells and/or hematopoietic cells to, e.g., suppress the proliferation of tumor cells, eliminate senescent cells, modulate pathogen infection (e.g., bacterial infection or viral infection) or inhibit pathogen infection, and uses thereof. In certain aspects, stem cells and/or NK cells provided herein lack expression of NKG2A and/or function, or show reduced expression and/or function of NKG2A. In certain other aspects, stem cells and/or NK cells provided herein comprise modified NKG2A. Methods of using cells of the present disclosure, e.g., in the treatment of cancer and infectious disease are also provided.

The present disclosure provides engineered cells (e.g., T cells) comprising a chimeric antigen receptor (CAR) and a therapeutic peptide, and methods of use thereof.

An aspect of the invention provides nucleic acids comprising a nucleotide sequence encoding chimeric antigen receptor (CAR) amino acid constructs. Polypeptides, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.

The present disclosure provides compounds and pharmaceutically acceptable salt thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic proteins.