Targeting T cells to tumor cells using bispecific antibodies

• The bispecific T cell engager (BiTE®) blinatumomab has demonstrated clear cut clinical activity.
• Three BiTE antibodies directed against solid tumor targets (EpCAM, CEA, PSMA) are under evaluation in the clinic.
• An increased understanding of the preclinical and clinical behavior of BiTE® antibodies will drive further clinical advances.
• Alternative immunotherapy formats that engage T cells or alter T cell immune function are under investigation.

The immune system, and in particular T cells, can be harnessed to treat cancer. Several bispecific T cell engaging antibodies of the BiTE® format are in early or late-stage clinical development. These small recombinant antibody constructs effectively trigger killing of cancer cells by temporarily attached, polyclonal T cells. Blinatumomab, a CD19/CD3-bispecific BiTE® antibody, has demonstrated high clinical activity in B cell leukemia and lymphoma patients. Three additional BiTE antibodies directed against surface target antigen expressed on solid tumors are being evaluated in phase I clinical trials. Alternative approaches to direct polyclonal T cells to kill cancer cells are under intense investigation.