Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the dual TACI-BCMA binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Provided herein are anti-CD24 antibodies that selectively bind human CD24 expressed in cancer cells, but not human CD24 expressed in non-cancerous cells, and the use of such antibodies in cancer therapy.

Methods are disclosed for treating a subject with a tumor. These methods include administering to the subject a therapeutically effective amount of CD8.sup.+CD39.sup.+CD103.sup.+ T cells. Methods also are disclosed for isolating a nucleic acid encoding a T cell receptor (TCR) that specifically binds a tumor cell antigen. These methods include isolating CD8.sup.+CD39.sup.+CD103.sup.+ T cells from a sample from a subject with a tumor expressing the tumor cell antigen, and cloning a nucleic acid molecule encoding a TCR from the CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In addition, methods are disclosed for expanding CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In additional embodiments, methods are disclosed for determining if a subject with a tumor will respond to a checkpoint inhibitor. The methods include detecting the presence of CD8.sup.+CD39.sup.+CD103.sup.+ T cells in a biological sample from a subject.

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and/or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

Provided herein are engineered immune cells, e.g. T cells, expressing a chimeric receptor comprising an intracellular region comprising a CD3zeta (CD3) signaling domain. In some embodiments, the engineered immune cells contain a modified CD247 locus that encodes the chimeric receptor or a portion thereof. In some embodiments, at least a portion of a CD3zeta chain encoded by CD247 genomic locus. Also provided are cell compositions containing the engineered immune cells, nucleic acids for engineering cells, and methods, kits and articles of manufacture for producing the engineered cells, such as by targeting a transgene encoding a portion of a chimeric receptor for integration into a region of a CD247 genomic locus. In some embodiments, the engineered cells, e.g. T cells, can be used in connection with cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered cells.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising V.sub.H having the amino acid sequence of SEQ ID NO: 3 and V.sub.L having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity against BCMA-positive tumor cells.

Provided herein are anti-CD24 antibodies that selectively bind human CD24 expressed in cancer cells but not human CD24 expressed in non-cancerous cells, and glycan-shielded epitopes to which they bind. Also provided are uses of such antibodies and peptides in cancer therapy.

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.

The present invention provides an anti-CD22 antibody molecule and a CD22-targeted chimeric antigen receptor (CAR) constructed using the anti-CD22 antibody molecule. The present invention also provides an application of the anti-CD22 antibody molecule and the CAR in the preparation of drugs for treating CD22-related diseases.

The present invention is directed to a monoclonal anti-human CS1 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 3 and VL having the amino acid of SEQ ID NO: 7. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.