Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer

Abstract

Various approaches of T-cell-based cancer immunotherapy are currently under investigation, among these are BiTE® (bispecific T-cell engager) antibody constructs, which have a unique design and mechanism of action. They are constructed by genetically linking onto a single polypeptide chain the minimal binding domains of monoclonal antibodies for tumor-associated surface antigens and for the T-cell receptor-associated molecule CD3. Concurrent engagement of the target cell antigen and CD3 leads to activation of polyclonal cytotoxic T-cells, resulting in target cell lysis. Blinatumomab, a BiTE targeting CD19, is being investigated in a broad range of B-cell malignancies and has recently been approved in the USA by the US FDA for Philadelphia chromosome-negative relapsed/refractory B-acute lymphoblastic leukemia under the trade name BLINCYTO™. The BiTE platform is one of the clinically most advanced T-cell immunotherapy options.

Keywords:

• bispecific antibody
• BiTE®
• blinatumomab
• cancer immunotherapy
• T-cells

Acknowledgments

The authors would like to thank Craig Kiefer (Amgen Inc.), for art work design and Beate Quednau, PhD (Amgen Inc.), for editorial support.

Declaration of interest

This paper has been funded by Amgen, Inc. J Stieglmaier is an employee of Amgen Research (Munich) GmbH and a shareholder in Amgen Inc. D Nagorsen is an employee of Amgen Inc., an inventor on blinatumomab-related patents and shareholder in Amgen Inc. J Benjamin is an employee of Amgen Inc. and a shareholder in Amgen Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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