Immune Modulating Antibody-Drug Conjugate (IM-ADC) for Cancer Immunotherapy

Lei He, Liangliang Wang, Zhisong Wang, Tiantian Li, Hui Chen, Yaning Zhang, Zeping Hu, Dimiter S. Dimitrov, Juanjuan Du, Xuebin Liao

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Antibody-drug conjugate (ADC) and immune checkpoint blockade (ICB) offer promising approaches for cancer treatment. Here, we describe an ADC constructed by conjugating anti-PD-L1 THIOMAB with a bifunctional immunomodulator D18 via a redox-cleavable linker. The resulting ADC HE-S2 not only triggers a potent antitumor immune response by blocking the PD-1/PD-L1 interaction and activating the Toll-like receptor 7/8 (TLR7/8) signaling pathway but also upregulates its targeted PD-L1 expression via epigenetic regulation and/or IFN-γinduction, thus conferring more sensitivity to the PD-1/PD-L1 blockade. We identify that ADC HE-S2 treatment could lead to more pronounced tumor suppression than the treatment of D18 in combination with the anti-PD-L1 antibody. Accordingly, this study provides a novel ADC strategy to enhance the antitumor immune response to ICB therapy.

Original languageEnglish (US)
Pages (from-to)15716-15726
Number of pages11
JournalJournal of Medicinal Chemistry
Volume64
Issue number21
DOIs
StatePublished - Nov 11 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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