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.