Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors

Jim Middelburg ¹, Kristel Kemper ², Patrick Engelberts ², Aran F Labrijn ², Janine Schuurman ², Thorbald van Hall ¹

Affiliations

¹ Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
² Genmab, 3584 CT Utrecht, The Netherlands.

PMID: 33466732
199 References
10 citations

Abstract

Immunotherapy of cancer with CD3-bispecific antibodies is an approved therapeutic option for some hematological malignancies and is under clinical investigation for solid cancers. However, the treatment of solid tumors faces more pronounced hurdles, such as increased on-target off-tumor toxicities, sparse T-cell infiltration and impaired T-cell quality due to the presence of an immunosuppressive tumor microenvironment, which affect the safety and limit efficacy of CD3-bispecific antibody therapy. In this review, we provide a brief status update of the CD3-bispecific antibody therapy field and identify intrinsic hurdles in solid cancers. Furthermore, we describe potential combinatorial approaches to overcome these challenges in order to generate selective and more effective responses.

Keywords: CD3-bispecific antibody; T-cell co-stimulation; T-cell engager; antibody therapy; immuno-oncology; on-target off-tumor toxicity; solid tumors; tumor-associated antigens.

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