Abstract: The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to the combined use of a PD-1 inhibitor, a TGF? inhibitor, and an adenosine inhibitor to treat cancer.

Abstract: The invention is based, in part, upon the discovery of a family of antibodies that specifically bind human T Cell Immunoglobulin and Mucin Domain-3 (TIM-3). The antibodies contain TIM-3 binding sites based on the CDRs of the antibodies. The antibodies can be used as therapeutic agents as a monotherapy or in combination with another therapeutic agent. When used as therapeutic agents, the antibodies can be optimized, e.g., affinity-matured, to improve biochemical and/or biophysical properties and/or to reduce or eliminate immunogenicity, when administered to a human patient. The antibodies inhibit TIM-3 from binding to TIM-3 ligands, e.g., galectin-9, phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). The disclosed antibodies can be used to inhibit the proliferation of tumor cells in vitro or in vivo. When administered to a human cancer patient or an animal model, the antibodies inhibit or reduce tumor growth in the human patient or animal model.

Abstract: The invention is based, in part, upon the discovery of a family of antibodies that specifically bind human T Cell Immunoglobulin and Mucin Domain-3 (TIM-3). More specifically, this invention relates to a method of treating cancer by administering an anti-TIM-3 antibody in combination with an anti-PD-L1/TGF? Trap fusion protein. When administered to a human cancer patient or an animal model, the antibodies inhibit or reduce tumor growth in the human patient or animal model.