Translation and Clinical Development of Bispecific T-cell Engaging Antibodies for Cancer Treatment.
Bispecific T-cell Engagers (BiTE®) antibody constructs enable a polyclonal T-cell response to cell-surface tumor-associated antigens, bypassing the narrow specificities of T-cell receptors and the need for antigen presentation through the major histocompatibility complex pathways. Blinatumomab, a CD19xCD3 BiTE® antibody construct, received accelerated approval for the treatment of relapsed/refractory Philadelphia chromosome negative acute lymphoblastic leukemia. Herein we review the pharmacology, safety, and efficacy observed in studies of blinatumomab and other BiTE® antibody constructs. Quantitative systems pharmacology is envisioned as a means to optimize dosing decisions for trials in which BiTE® antibody constructs are administered as monotherapy or in combination with other immunotherapies.
Clinical Pharmacology, Modeling, and Simulation, Amgen Inc., Thousand Oaks, California, USA.
T
T
Yuraszeck
Clinical Pharmacology, Modeling, and Simulation, Amgen Inc., Thousand Oaks, California, USA.
S
S
Kasichayanula
Global Development, Oncology, Amgen Inc., Thousand Oaks, California, USA.
J E
JE
Benjamin
D018033:Antibodies, Bispecific / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000494:pharmacology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm; D000954:Antigens, Surface; C510808:blinatumomab