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Targeting T Cells with Bispecific Antibodies for Cancer Therapy

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Abstract

Bispecific antibodies (BiAbs) offer a unique opportunity to redirect immune effector cells to kill cancer cells. BiAbs combine the benefits of different binding specificities of two monoclonal antibodies (mAbs) into a single construct. This unique feature of BiAbs enables approaches that are not possible with single mAbs. Advances in antibody engineering and antigen profiling of malignant cells have led to the development of a number of BiAb formats and their combinations for redirecting effector cells to tumor targets. There have been significant advances in the design and application of BiAbs for intravenous and local injection.The initial barrier of cytokine storm has been partially overcome by more recent constructs that have improved clinical effectiveness without dose-limiting toxicities. Since the recent revival of BiAbs, there has been multiple, ongoing, phase I/II and III trials, and some promising clinical outcomes have been reported in completed clinical studies. This review focuses on arming T cells with BiAbs to create the ‘poor man’s cytotoxic lymphocyte’.

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Acknowledgments

We appreciate the efforts of the physicians, immunotherapy technical staff, clinical coordinators, nursing staff, administrative staff, and the leadership of the Barbara Ann Karmanos Cancer Institute and Roger Williams Medical Center. Special thanks to Wendy Young, Annette Olson, Lori Hall, Patricia Steele, and Karen Myers for their dedicated efforts to serve the immunotherapy patients. The studies were supported by NIH grants R01 CA 092344 (LGL), R01 CA 140314 (LGL); Cancer Center Support Grant P30 CA022453-25; Translational Grants #6092-09 (LGL) and #6066-06 (LGL) from the Leukemia and Lymphoma Society; Susan G. Komen Foundation grant BCTR0707125 (LGL); startup funds from the Karmanos Cancer Institute (LGL); and a gift from the Bill Young Foundation for breast cancer immunotherapy (LGL). LGL is a founder of Transtarget, Inc. AT has no conflict of interest.

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  1. Department of Oncology, Wayne State University and Barbara Ann Karmanos Cancer Center, Detroit, MI, USA

    Lawrence G. Lum & Archana Thakur

  2. Department of Medicine, Wayne State University and Barbara Ann Karmanos Cancer Center, Detroit, MI, USA

    Lawrence G. Lum

  3. Department of Immunology and Microbiology, Wayne State University and Barbara Ann Karmanos Cancer Center, Detroit, MI, USA

    Lawrence G. Lum

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  1. Lawrence G. Lum
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Correspondence to Lawrence G. Lum.

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Lum, L.G., Thakur, A. Targeting T Cells with Bispecific Antibodies for Cancer Therapy. BioDrugs 25, 365–379 (2011). https://doi.org/10.2165/11595950-000000000-00000

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