Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma.

The use of specific anti-tumor antibodies has transformed the solid cancer therapeutics landscape with the relative successes of therapies such as anti-HER2 in breast cancer, and anti-EGFR in HNSCC and colorectal cancer. However, these therapies result in toxicity and the emergence of resistant tumors. Here, we showed that removing immune suppression and enhancing stimulatory signals increased the anti-tumor activity of unmodified TA99 antibodies (anti-TYRP1) with a significant reduction of growth of solid tumors and lung metastases in mouse models of melanoma.

Redirected T Cell Cytotoxicity in Cancer Therapy.

Bispecific antibodies that recruit and redirect T cells to attack tumor cells have tremendous potential for the treatment of various malignancies. In general, this class of therapeutics, known as CD3 bispecifics, promotes tumor cell killing by cross-linking a CD3 component of the T cell receptor complex with a tumor-associated antigen on the surface of the target cell. Importantly, this mechanism does not rely on a cognate interaction between the T cell receptor and a peptide:HLA complex, thereby circumventing HLA (human leukocyte antigen) restriction.