BiTE: Teaching antibodies to engage T-cells for cancer therapy.
Bispecific T-cell-engager (BiTE) antibodies are designed to transiently engage cytotoxic T-cells for lysis of selected target cells. Although this therapeutic concept had been proposed more than two decades ago, BiTE, and also trispecific, antibodies did not achieve clinical proof-of-concept until the past 2 years. Their clinical activity corroborates findings that ex vivo expanded, autologous T-cells derived from tumor tissue, or transfected with specific T-cell receptors, have shown therapeutic potential in the treatment of solid tumors. While these personalized approaches prove that T-cells alone can have considerable therapeutic activity, even in late-stage cancer, they are cumbersome to perform on a broad basis. This is different for cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies, which facilitate generation of tumor-specific T-cell clones, and also for bi- and tri-specific antibodies that directly engage a large proportion of patients' T-cells for cancer cell lysis. The potential of global T-cell engagement for human cancer therapy by T-cell-engaging antibodies has yet to be fully investigated.
Baeuerle
Patrick A
PA
Micromet Inc, 6707 Democracy Boulevard, Suite 505, Bethesda, MD 20817, USA. patrick.baeuerle@micromet-inc.com
Kufer
Peter
P
Bargou
Ralf
R
D018033:Antibodies, Bispecific / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human