PDF(Pubmed)
Abstract：
Immune checkpoint therapy (ICT) for cancer can yield dramatic clinical responses; however, these may only be observed in a minority of patients. These responses can be further limited by subsequent disease recurrence and resistance. Combination immunotherapy strategies are being developed to overcome these limitations. We have previously reported enhanced efficacy of combined intratumoral cowpea mosaic virus immunotherapy (CPMV IIT) and ICT approaches. Lymphocyte-activation gene-3 (LAG-3) is a next-generation inhibitory immune checkpoint with broad expression across multiple immune cell subsets. Its expression increases on activated T cells and contributes to T cell exhaustion. We observed heightened efficacy of a combined CPMV IIT and anti-LAG-3 treatment in a mouse model of melanoma. Further, LAG-3 expression was found to be increased within the TME following intratumoral CPMV administration. The integration of CPMV IIT with LAG-3 inhibition holds significant potential to improve treatment outcomes by concurrently inducing a comprehensive anti-tumor immune response, enhancing local immune activation, and mitigating T cell exhaustion.
摘要：
癌症的免疫检查点疗法（ICT）可以产生巨大的临床反应；然而，这些可能只在少数患者中观察到。这些反应可进一步受到随后的疾病复发和抗性的限制。正在开发组合免疫疗法策略以克服这些限制。我们以前曾报道过瘤内cow豆花叶病毒免疫疗法（CPMVIIT）和ICT方法的联合功效增强。淋巴细胞活化基因-3(LAG-3)是下一代抑制性免疫检查点,其在多个免疫细胞亚群中具有广泛表达。其表达在活化的T细胞上增加并有助于T细胞耗尽。我们在黑素瘤的小鼠模型中观察到CPMVIIT和抗LAG-3联合治疗的功效增强。Further,发现瘤内CPMV施用后TME内的LAG-3表达增加。CPMVIIT与LAG-3抑制的整合具有通过同时诱导全面的抗肿瘤免疫反应来改善治疗结果的显着潜力。增强局部免疫激活，减轻T细胞衰竭。
