TY - JOUR
T1 - T-cell-engaging bispecific antibodies in cancer
AU - van de Donk, Niels W. C. J.
AU - Zweegman, Sonja
N1 - Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/7/8
Y1 - 2023/7/8
N2 - T-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.
AB - T-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.
UR - http://www.scopus.com/inward/record.url?scp=85162908295&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(23)00521-4
DO - https://doi.org/10.1016/S0140-6736(23)00521-4
M3 - Review article
C2 - 37271153
SN - 0140-6736
VL - 402
SP - 142
EP - 158
JO - The Lancet
JF - The Lancet
IS - 10396
ER -