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Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells.
- Source :
-
Nature biomedical engineering [Nat Biomed Eng] 2021 Nov; Vol. 5 (11), pp. 1261-1273. Date of Electronic Publication: 2021 Nov 01. - Publication Year :
- 2021
-
Abstract
- Bispecific T-cell engagers (BiTEs) preferentially targeting tumour-associated antigens and stimulating CD3-mediated signalling are being used in patients to treat acute B-cell lymphoblastic leukemia. However, the potency of BiTEs in solid tumours is limited by their short half-life and their severe toxicity at relevant therapeutic doses. Here we report the design and in vivo performance of a bispecific antibody that simultaneously targets the murine T-cell co-receptor CD3ε and the murine immune checkpoint programmed-death ligand 1 (PD-L1). In multiple syngeneic tumour models, the bispecific antibody generated higher antitumour immune responses than conventional BiTEs targeting tumour-associated antigens and CD3ε. We found that the durable antigen-specific T-cell responses resulted from the rejuvenation of CD8 T cells, owing to the blockade of PD-L1 on dendritic cells (but not on tumour cells) and co-stimulation by B7-1&2 (a peripheral membrane protein on dendritic cells). Bispecific T-cell engagers targeting dendritic cells rather than tumour cells may represent a general means of T-cell rejuvenation for durable cancer immunotherapy.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Details
- Language :
- English
- ISSN :
- 2157-846X
- Volume :
- 5
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nature biomedical engineering
- Publication Type :
- Academic Journal
- Accession number :
- 34725504
- Full Text :
- https://doi.org/10.1038/s41551-021-00800-2