CU06-1004-Induced Vascular Normalization Improves Immunotherapy by Modulating Tumor Microenvironment via Cytotoxic T Cells

Songyi Park, Ji Hoon Oh, Dong Jin Park, Haiying Zhang, Minyoung Noh, Yeomyung Kim, Ye Seul Kim, Hyejeong Kim, Young Myeong Kim, Sang Jun Ha, Young Guen Kwon

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, the usage of a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types of cancer. Especially, vascular abnormal structures of which deter delivery route by leakage and cause the poor perfusion were considered to be environment unfavorable to T cells and immune checkpoint blockade (ICB) delivery within the tumor microenvironment (TME). Herein, we report stabilization of tumor blood vessels by endothelial dysfunctional blocker CU06-1004, which modified the TME and showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged the survival of tumor-bearing mice by decreasing tumor growth. T-cell infiltration increased in the tumors of the combination group, with cytotoxic CD8+ T cell activity within the tumor parenchyma upregulated compared with anti-PD-1 monotherapy. Tumor inhibition was associated with reduced hypoxia and reduced vessel density in the central region of the tumor. These effects correlated significantly with enhanced expression of IFN gamma and PD-L1 in tumors. Taken together, our findings suggest that CU06-1004 is a potential candidate drug capable of improving therapeutic efficacy of anti-PD-1 through beneficial changes in the TME.

Original languageEnglish
Article number620166
JournalFrontiers in Immunology
Volume11
DOIs
Publication statusPublished - 2021 Jan 26

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Park, Oh, Park, Zhang, Noh, Kim, Kim, Kim, Kim, Ha and Kwon.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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