Cowpea Mosaic Virus and Natural Killer Cell Agonism for In Situ Cancer Vaccination,Nano Letters

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Cowpea Mosaic Virus and Natural Killer Cell Agonism for In Situ Cancer Vaccination
Nano Letters ( IF 9.6 ) Pub Date : 2022-06-17 , DOI: 10.1021/acs.nanolett.2c01328
Edward C Koellhoffer ₁ , Nicole F Steinmetz _{1,

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Affiliation

We have previously shown the plant virus Cowpea mosaic virus (CPMV) to be an efficacious in situ cancer vaccine, providing elimination of tumors and tumor-specific immune memory. Additionally, we have shown that CPMV recruits Natural Killer (NK) cells within the tumor microenvironment. Here we aimed to determine whether a combination of CPMV and anti-4-1BB monoclonal antibody agonist to stimulate tumor-resident and CPMV-recruited NK cells is an effective dual therapy approach to improve NK cell function and in situ cancer vaccination efficacy. Using murine models of metastatic colon carcinomatosis and intradermal melanoma, intratumorally administered CPMV + anti-4-1BB dual therapy provided a robust antitumor response, improved elimination of primary tumors, and reduced mortality compared to CPMV and anti-4-1BB monotherapies. Additionally, on tumor rechallenge there was significant delay/prevention of tumor development and improved survival, highlighting that the CPMV + anti-4-1BB dual therapy enables potent and durable antitumor efficacy.

中文翻译：

用于原位癌症疫苗接种的豇豆花叶病毒和自然杀伤细胞激动剂

我们之前已经证明植物病毒豇豆花叶病毒 (CPMV) 是一种有效的原位癌症疫苗，可以消除肿瘤和肿瘤特异性免疫记忆。此外，我们已经证明 CPMV 在肿瘤微环境中招募自然杀伤 (NK) 细胞。在这里，我们旨在确定 CPMV 和抗 4-1BB 单克隆抗体激动剂联合刺激肿瘤驻留和 CPMV 募集的 NK 细胞是否是改善 NK 细胞功能和原位癌症疫苗接种功效的有效双重治疗方法。使用转移性结肠癌和皮内黑色素瘤的小鼠模型，与 CPMV 和抗 4-1BB 单一疗法相比，肿瘤内施用 CPMV + 抗 4-1BB 双重疗法提供了强大的抗肿瘤反应，改善了原发性肿瘤的消除并降低了死亡率。此外，

更新日期：2022-06-17

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