首页|Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects

Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects

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Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years,but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone.In this study,an oncolytic virus(rVSV-LCMVG)that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells.By transforming the immunosuppressive tumor microenvironment into an immunosensitive one,in B16 tumor-bearing mice,combination therapy showed superior antitumor effects than monotherapy.This occurred whether the OV was administered intratumorally or intravenously.Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8+T cells to the TME to trigger antitumor immune responses.Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment,down-regulating the expression of PD-1,and restoring effector T-cell function.To offer a combination therapy with greater translational value,mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells.The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival.This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens,in terms of synergistic efficacy and mechanism.

Rao Fu、Ruoyao Qi、Hualong Xiong、Xing Lei、Yao Jiang、Jinhang He、Feng Chen、Liang Zhang、Dekui Qiu、Yiyi Chen、Meifeng Nie、Xueran Guo、Yuhe Zhu、Jinlei Zhang、Mingxi Yue、Jiali Cao、Guosong Wang、Yuqiong Que、Mujing Fang、Yingbin Wang、Yixin Chen、Tong Cheng、Shengxiang Ge、Jun Zhang、Quan Yuan、Tianying Zhang、Ningshao Xia

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State Key Laboratory of Vaccines for Infectious Diseases,Xiang An Biomedicine Laboratory,Department of Laboratory Medicine,School of Public Health & School of Life Sciences,Xiamen University,Xiamen 361102 Fujian,China

National Institute of Diagnostics and Vaccine Development in Infectious Diseases,Xiamen 361102 Fujian,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central Universities

823220278234104332170943819914913230074420720220003

2024

10.1038/s41392-024-01824-1

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

CSTPCD
ISSN：
年,卷(期)：2024.9(6)