Sarivalasis Apostolos, Morotti Matteo, Mulvey Arthur, Imbimbo Martina, Coukos George
Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
CHUV, Rue du Bugnon 46, Lausanne BH09-701, Switzerland.
Ther Adv Med Oncol. 2021 Apr 22;13:17588359211008399. doi: 10.1177/17588359211008399. eCollection 2021.
Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated , and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy.
上皮性卵巢癌(EOC)是妇科癌症相关死亡的最重要原因。尽管医学治疗有所改进,特别是在纳入针对同源重组缺陷的药物后,EOC的生存率仍然很低。过继性细胞疗法(ACT)是一种个性化免疫疗法,其中自体淋巴细胞被扩增、操控,然后重新注入患者体内以介导癌症排斥反应。这种极具前景且具有治愈潜力的新方法包含多种策略,包括过继性转移肿瘤浸润淋巴细胞、自然杀伤细胞,或工程化免疫组件,如嵌合抗原受体(CAR)构建体和工程化T细胞受体。基因组学和免疫工程学的技术进步使基于新抗原的ACT策略以及具有增强细胞持久性和肿瘤内迁移能力的CAR-T细胞成为可能,这有可能为EOC患者拓宽机会。此外,基于树突状细胞的免疫疗法已在EOC患者中进行测试,取得了适度但令人鼓舞的结果,而基于DC的疫苗接种作为其他癌症疗法的启动方式的联合应用也显示出令人鼓舞的结果。在本手稿中,我们提供了以临床为导向的各种形式细胞疗法治疗EOC的历史概述,重点是T细胞疗法。