The present disclosure is directed to the use of modified NK cells for immunotherapy in combination with an antibody, or antigen-binding fragment thereof, to induce an enhanced antibody-dependent cellular cytotoxicity (ADCC) effect.

Provided herein are anti-DLL3 chimeric antigen receptors (CARs), DLL3 binding proteins and uses of such CARs or DLL3 binding proteins in the treatment of DLL3 associated disorders, such as small cell lung cancer.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF- trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the GPC3 binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Provided herein are anti-DLL3 chimeric antigen receptors (CARs), DLL3 binding proteins and uses of such CARs or DLL3 binding proteins in the treatment of DLL3 associated disorders, such as small cell lung cancer.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Aspects of the disclosure relate to polypeptides comprising a signal peptide, an antigen-binding domain that specifically binds TGF-, a peptide spacer, a transmembrane domain, and an endodomain. When expressed in a cell, the polypeptides are capable of not only neutralizing the TGF- but also specifically triggering T-cell activation in the presence of TGF-. T-cell activation spurs the immune cell to produce immunostimulatory cytokines and proliferate, thus turning TGF- from an immunosuppressive signal to an activating stimulus.