Translation and Clinical Development of Bispecific T-cell Engaging Antibodies for Cancer Treatment

双特异性T细胞接合抗体在癌症治疗中的转化和临床开发

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Abstract

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.

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