Cody C Gowan, Mee Y Bartee, Erica Flores, Bulent A Aksoy, Conor Templeton, Kati Baillie, Myroslawa Happe, Eric Bartee
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引用次数: 0
摘要
T细胞免疫球蛋白和粘蛋白结构域3(TIM3)正在成为基于抗体的检查点阻断疗法的潜在靶点。然而,TIM3阻断与其他治疗方式相结合的疗效尚未得到广泛研究。在目前的研究中,我们将 TIM3 阻断与基于肌瘤病毒的溶瘤病毒疗法(OV)相结合。我们的研究结果表明,肌瘤病毒启动巨大抗肿瘤免疫反应的能力与TIM3阻断将肿瘤微环境转变为更多促炎状态的能力相辅相成。因此,TIM3 阻断与 OV 的联合疗法能够彻底根除既定疾病,而单一疗法均无效。这些数据首次证明了 OV 可以增强 TIM3 阻断的疗效,并表明这种疗法可能需要被纳入更具侵略性的组合疗法中,以发挥其作为免疫疗法的潜力。
The Combination of TIM3-Based Checkpoint Blockade and Oncolytic Virotherapy Regresses Established Solid Tumors.
T-cell immunoglobulin and mucin domain 3 (TIM3) is emerging as a potential target for antibody-based checkpoint blockade. However, the efficacy of TIM3 blockade in combination with other treatment modalities, has not been extensively studied. In the current work we combined TIM3 blockade with myxoma virus-based oncolytic virotherapy (OV). Our results demonstrate that myxoma virus's ability to initiate an immense antitumor immune response complements the ability of TIM3 blockade to shift the tumor microenvironment to a more proinflammatory state. As a result, the combination of TIM3 blockade and OV is able to completely eradicate established disease, while neither monotherapy is effective. These data represent the first demonstration that OV can enhance the efficacy of TIM3 blockade and suggest that this treatment may need to be incorporated into more aggressive, combinatorial regimens in order to fulfill its potential as an immunotherapeutic.
期刊介绍:
Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.