The present disclosure provides methods of producing hybrid Th1/Th17 cells. Also provided herein are methods of treating cancer comprising targeting the CD38-mediated metabolic axis.

The subject matter disclosed herein is generally directed to modulating T cell dysfunctional and effector states by modulating glucocorticoid and IL-27 signaling. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from the differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20/anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.

Provided is an GARP protein antibody, and a cell comprising or expressing the GA RP protein antibody. The GARP protein antibody binds to human GARP/human TGF-?1 complex with a K.sub.D value of about 1.0E-12 or less. Also provided are a pharmaceutical combination comprising the GARP protein antibody and an immune checkpoint inhibitor and use thereof.

The present invention concerns antigen binding proteins specifically binding melanoma associated antigen A (MAGE-A) protein-derived antigens. The invention in particular provides antigen binding proteins which specifically bind to the MAGE-A antigenic peptide comprising or consisting of SEQ ID NO: 1 in a complex with a major histocombatibility (MHC) protein. The antigen binding proteins of the invention contain, in particular, the complementary determining regions (CDRs) of novel engineered T cell receptors (TCRs) that specifically bind to said MAGE-A peptide/MHC complex. The antigen binding proteins of the invention are of use for the diagnosis, treatment and prevention of MAGE-A expressing cancerous diseases. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins of the invention.

Provided herein are recombinant nucleic acids encoding a T cell receptor (TCR) fusion protein (TFP) and an interleukin-15 (IL-15) polypeptide and/or an interleukin-15 receptor alpha (IL-15R?) polypeptide, modified T cells expressing the encoded molecules, and methods of use thereof for the treatment of diseases, including cancer.

An engineered immune receptor (e.g., a chimeric antigen receptor (CAR) or chimeric costimulatory receptor (CCR)) that contains one or more short linear motifs that bind to other intracellular signaling proteins are provided, as well as nucleic acids encoding the same, cells that contain the same and methods of use. Examples of such motifs include a PLC?1-binding motifs and TRAF binding motifs, but other motifs may be used. These motifs are thought to recruit other proteins to the engineered immune receptor, thereby altering cellular responses.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.