Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells

Longchao Liu, Jiahui Chen, Joonbeom Bae, Huiyu Li, Zhichen Sun, Casey Moore, Eric Hsu, Chuanhui Han, Jian Qiao, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1261-1273
Number of pages13
JournalNature Biomedical Engineering
Volume5
Issue number11
DOIs
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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