瑞典隆德大学
研究人员开发了一种通过腺病毒递送转录因子PU.1、IRF8和BATF3，在体内对肿瘤细胞进行重编程的方法，使其能够作为1型常规树突状细胞呈递抗原。
重编程的肿瘤细胞重塑了其肿瘤微环境，招募并扩增了多克隆细胞毒性T细胞，诱导了肿瘤退缩，并在多种小鼠黑色素瘤模型中建立了长期系统性免疫。
在人类肿瘤球体和异种移植模型中，向免疫原性树突状细胞样细胞的重编程过程不受通常限制免疫疗法的免疫抑制的影响。
该研究为体内免疫细胞重编程的癌症免疫疗法的人体临床试验铺平了道路。
研究人员表示，免疫疗法可以为部分癌症患者带来长期生存机会，但其普遍成功受到抗原呈递不足以及免疫原性细胞被排除在肿瘤微环境之外的限制。
附：英文原文
Title: In vivo dendritic cell reprogramming for cancer immunotherapy
Author: Ervin Ascic, Fritiof kerstrm, Malavika Sreekumar Nair, André Rosa, Ilia Kurochkin, Olga Zimmermannova, Xavier Catena, Nadezhda Rotankova, Charlotte Veser, Michal Rudnik, Tommaso Ballocci, Tiffany Schrer, Xiaoli Huang, Maria de Rosa Torres, Emilie Renaud, Marta Velasco Santiago, zcan Met, David Askmyr, Malin Lindstedt, Lennart Greiff, Laure-Anne Ligeon, Irina Agarkova, Inge Marie Svane, Cristiana F. Pires, Fábio F. Rosa, Carlos-Filipe Pereira
Issue&Volume: 2024-09-05
Abstract: Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells, induced tumor regressions, and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.
DOI: adn9083
Source: https://www.science.org/doi/10.1126/science.adn9083