Enhanced anti-tumor reactivity of cytotoxic T lymphocytes expressing PD-1 decoy

Jae Hun Shin, Hyung Bae Park, Kyungho Choi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γsecretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

Original languageEnglish
Pages (from-to)134-139
Number of pages6
JournalImmune Network
Volume16
Issue number2
DOIs
Publication statusPublished - 2016

Bibliographical note

Funding Information:
We thank Drs. Yosef Refaeli and Garry Nolan for providing us valuable materials. This work was supported by grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2013R1A2A2A01009444), Republic of Korea.

Publisher Copyright:
© 2016, Korean Association of Immunologists. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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