谷歌浏览器插件
订阅小程序
在清言上使用

Local Therapy with an Engineered Oncolytic Adenovirus Enables Antitumor Response in Non-Injected Melanoma Tumors in Mice Treated with Apd-1

ONCOIMMUNOLOGY(2022)

引用 12|浏览20
暂无评分
摘要
Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 ("virus"). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors' response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer.
更多
查看译文
关键词
Oncolytic adenovirus,immunotherapy,TNFa,IL-2,aPD-1,lymphocytes,melanoma
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要