| abstract |
The present invention is based, in part, on the discovery of a family of antibodies that specifically bind human T cell immunoglobulin and mucin domain 3 (TIM-3). The antibody comprises a TIM-3 binding site based on the CDRs of the antibody. The antibodies can be used as a therapeutic agent for monotherapy or in combination with another therapeutic agent. When used as a therapeutic agent, the antibody may 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. Antibodies inhibit TIM-3 binding to TIM-3 ligands, e.g., galectin-9, phosphatidylserine (PtdSer), and carcinoembryonic antigen-associated cell adhesion molecule 1(CEACAM 1). The disclosed antibodies can be used to inhibit the proliferation of tumor cells in vitro or in vivo. The antibody inhibits or reduces tumor growth in a human patient or an animal model when administered to the human patient or animal model. |