A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects

Wei Yun Lai, Bo Tsang Huang, Jen Wei Wang, Pei Ying Lin, Pan Chyr Yang

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The PD-1/PD-L1 axis is a major pathway involved in tumor immune evasion. Here, we report the novel PD-L1 antagonizing DNA aptamer (aptPD-L1) and demonstrate an integrated pipeline that expedites therapeutic aptamer development. Aptamer can exert antibody-mimic functions and is advantageous over antibody for its chemically synthetic nature, low immunogenicity, and efficient tissue penetration. Our results showed that aptPD-L1 blocked the binding between human PD-1 and PD-L1. Experiments using murine models showed that aptPD-L1 promoted in vitro lymphocyte proliferation and suppressed in vivo tumor growth without the induction of observable liver or renal toxicity. Analyses on the aptPD-L1-treated tumors further revealed elevated levels of infiltrating CD4+ and CD8+ T cells, intratumoral IL-2, TNF-α, interferon (IFN)-γ and the C-X-C motif chemokines, CXCL9 and CXCL10. The CD8+ T cells in the aptPD-L1-treated tumors had higher CXCR3 expression level compared to the random-sequence oligonucleotides-treated ones. Besides, the length and density of CD31+ intratumoral microvessels were significantly decreased in the aptPD-L1 treatment group. Collectively, our data suggested that aptPD-L1 helps T cell function restoration and modifies tumor microenvironment. These chemokines might orchestrate together to attract more T cells into the tumor tissues to form the positive amplification loop against tumor growth, indicating the translational potential of aptPD-L1 in cancer immunotherapy.

Original languageEnglish
Pages (from-to)e397
JournalMolecular Therapy - Nucleic Acids
Volume5
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • aptamer
  • immunotherapy
  • PD-1
  • PD-L1
  • tumor microenvironment

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint

Dive into the research topics of 'A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects'. Together they form a unique fingerprint.

Cite this