Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment
Authors:
Open Access
- 9 February 2017
- journal article
- review article
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 101 (5) , 634-645
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.Keywords
This publication has 83 references indexed in Scilit:
- Targeting T cells to tumor cells using bispecific antibodiesCurrent Opinion in Chemical Biology, 2013
- Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALLBlood, 2012
- CD19: a biomarker for B cell development, lymphoma diagnosis and therapyExperimental Hematology & Oncology, 2012
- Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantationBlood, 2012
- Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007Blood, 2012
- Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T‐cellsBritish Journal of Pharmacology, 2010
- Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impairedBlood, 2009
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002
- Use of Tumor-Infiltrating Lymphocytes and Interleukin-2 in the Immunotherapy of Patients with Metastatic MelanomaNew England Journal of Medicine, 1988
- Treatment of B-Cell Lymphoma with Monoclonal Anti-Idiotype AntibodyNew England Journal of Medicine, 1982