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T-cell-engaging bispecific antibodies in cancer.
- Source :
-
Lancet . Jul2023, Vol. 402 Issue 10396, p142-158. 17p. - Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01406736
- Volume :
- 402
- Issue :
- 10396
- Database :
- Academic Search Index
- Journal :
- Lancet
- Publication Type :
- Academic Journal
- Accession number :
- 164862207
- Full Text :
- https://doi.org/10.1016/S0140-6736(23)00521-4