Various TnMUC1-specific chimeric antigen receptors (CARs), nucleic acids encoding the same, and methods of using the same, are provided. Compositions and methods comprising a TnMUC1-specific CAR for treating MUC1-associated cancer in a subject in need thereof are provided.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Provided herein are chimeric switch receptors (CSRs) comprising an ectodomain and/or transmembrane domain derived from an inhibitory receptor (e.g. PD1 or TGFβR2) fused to the transmembrane domain and/or intracellular signaling domain derived from one or more costimulatory proteins (e.g. CD2, CD28, MyD88, DAP10 or ICOS), or variants thereof. The chimeric switch receptors are designed to convert a signal e.g. an inhibitory signal such as an immunosuppressive signal in the form of PD-L1 or TGFβ into a costimulatory signal. Also provided are engineered immune cells engineered to functionally express a chimeric switch receptor and/or a CAR and optionally also a chimeric cytokine receptor (CCR), and populations thereof, methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating e.g. cancer (e.g. solid or hematologic tumors) by administering the cells and the compositions.

A nucleic acid construct and mammalian cell harboring nucleic acids encoding an anti-CD7 chimeric antigen receptor are provided. Methods for treating cancer, in particular a hematologic cancer, using the nucleic acid construct or mammalian cell are also described.

The present invention relates to a human CD123-targeting chimeric receptor ligand, comprising an IL-3 molecule-based CD123 binding domain, a transmembrane region, and an intracellular signaling domain. The present invention provides a T cell modified by the human CD123-targeting chimeric receptor ligand and capable of specifically binding with CD123 on tumor cell surfaces, thereby having specific cytotoxicity on tumor cells. The present invention further relates to an application of the human CD123-targeting chimeric receptor ligand and an immune effector cell thereof in preparing an anti-tumor immunotherapy drug.

The present disclosure generally relates to, inter alia, novel chimeric polypeptides and chimeric antigen receptors (CARs) that include a hinge domain from CD28 and optionally a costimulatory domain not from CD28. The disclosure also provides compositions and methods useful for producing such molecules, as well as methods for the detection and treatment of diseases, such as cancer.

The present application relates to functionally optimized intracellular co-stimulatory domains, optionally in combination with cell-intrinsic immune checkpoint inhibitory receptors or immune-stimulatory receptors or portions thereof, which can be used in adoptive cell therapy to treat human diseases and disorders.

This disclosure provides modified recombinant retroviruses comprisings containing a 2A-peptide or peptide-like coding sequence operably linked to a heterologous polynucleotide. The disclosure further relates to cells and vector expressing or comprising such vectors and methods of using such modified vectors in the treatment of disease and disorders.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.