Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

Elhag, Osama A.O.; Hu, Xiao-Jing; Wen-Ying, Zhang; Li, Xiong; Yuan, Yong-Ze; Deng, Ling-Feng; Liu, De-Li; Liu, Ying-Le; Hui, Geng

추천

검색

자료유형: 학술저널

저자정보: Elhag, Osama A.O. (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Hu, Xiao-Jing (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Wen-Ying, Zhang (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Li, Xiong (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Yuan, Yong-Ze (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Deng, Ling-Feng (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Liu, De-Li (Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University) Liu, Ying-Le (The State Key Laboratory of Virology, College of Life Sciences, Wuhan University) Hui, Geng (Hubei Key Laboratory)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제13권 제8호

발행연도: 2012.1

수록면: 4,031 - 4,036 (6page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

#PD-1 #sPD-1 #B7H1 #gene therapy #tumor immunotherapy

참고문헌 (0)

참고문헌 신청

참고문헌이 DBpia에서 서비스 중이라면, [참고문헌 신청]을 통해 등록해보세요

이 논문의 저자 정보

Elhag, Osama A.O.

소속기관 Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Centra