通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The oncolytic virus VT09X optimizes immune checkpoint therapy in low immunogenic melanoma.
The oncolytic virus VT09X optimizes immune checkpoint therapy in low immunogenic melanoma.
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预先存在免疫细胞浸润水平低的肿瘤对免疫检查点治疗反应不佳。溶瘤病毒通过调节肿瘤微环境并影响癌症-免疫循环中的多个步骤来优化免疫治疗,使其成为联合策略中极具吸引力的药物。我们构建了一种基于HSV-1的溶瘤病毒,并在携带非免疫原性B16-F10黑色素瘤的hPD-1敲入小鼠中研究了其与已上市的PD-1抗体Keytruda(pembrolizumab)联合使用的抗肿瘤效果。我们的结果显示,肿瘤中CD8+和CD4+T细胞浸润、IFN-γ分泌及PD-L1表达增强,随后导致小鼠总生存期延长。外周血中也观察到淋巴细胞比例的全身性变化。总之,这些发现提供了证据,表明溶瘤病毒可被构建为联合治疗的潜在平台,特别是用于治疗对免疫检查点治疗反应不佳的肿瘤。
Tumors with a low level of pre-existing immune cell infiltration respond poorly to immune checkpoint therapies. Oncolytic viruses optimize immunotherapies by modulating the tumor microenvironment and affecting multiple steps in the cancer-immunity cycle, making them an attractive agent for combination strategies.
We engineered an HSV-1-based oncolytic virus and investigated its antitumor effects in combination with the marketed PD-1 antibody Keytruda (pembrolizumab) in hPD-1 knock-in mice bearing non-immunogenic B16-F10 melanoma.
Our results showed enhanced CD8 + and CD4 + T cell infiltration, IFN-γ secretion and PD-L1 expression in tumors, subsequently leading to the prolonged overall survival of mice. Systemic changes in lymphocyte cell proportions were also observed in the peripheral blood. In summary, these findings provide evidence that oncolytic viruses can be engineered as a potential platform for combination therapies, especially to treat tumors that are poorly responsive to immune checkpoint therapy.
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