• Lancet · Jul 2023

    Review

    T-cell-engaging bispecific antibodies in cancer.

    • van de DonkNiels W C JNWCJAmsterdam University Medical Centres, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands. Electronic address: n.vandedonk@amsterdamumc.nl. and Sonja Zweegman.
    • Amsterdam University Medical Centres, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands. Electronic address: n.vandedonk@amsterdamumc.nl.
    • Lancet. 2023 Jul 8; 402 (10396): 142158142-158.

    AbstractT-cell-engaging bispecific antibodies (BsAbs) simultaneously bind to antigens on tumour cells and CD3 subunits on T cells. This simultaneous binding results in the recruitment of T cells to the tumour, followed by T-cell activation and degranulation, and tumour cell elimination. T-cell-engaging BsAbs have shown substantial activity in several haematological malignancies by targeting CD19 in acute lymphoblastic leukaemia, CD20 in B-cell non-Hodgkin lymphoma, and BCMA and GPRC5D in multiple myeloma. Progress with solid tumours has been slower, in part due to the paucity of therapeutic targets with a tumour-specific expression profile, which is needed to limit on-target off-tumour side-effects. Nevertheless, BsAb-mediated recognition of a peptide fragment of gp100 presented by HLA-A2:01 molecules has shown marked activity in patients with unresectable or metastatic uveal melanoma. Cytokine release syndrome is the most frequent toxicity associated with BsAb treatment and is caused by activated T cells secreting proinflammatory cytokines. Understanding of resistance mechanisms has resulted in the development of new T cell-redirecting formats and novel combination strategies, which are expected to further improve depth and duration of response.Copyright © 2023 Elsevier Ltd. All rights reserved.

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