Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gynecol Oncol. 2024 Jul;186:77-84. doi: 10.1016/j.ygyno.2024.04.001. Epub 2024 Apr 10.
Although ovarian cancer patients typically respond to standard of care therapies, including chemotherapy and DNA repair inhibitors, the majority of tumors recur highlighting the need for alternative therapies. Ovarian cancer is an immunogenic cancer in which the accumulation of tumor infiltrating lymphocytes (TILs), particularly T cells, is associated with better patient outcome. Thus, harnessing the immune system through passive administration of T cells, a process called adoptive cell therapy (ACT), is a promising therapeutic option for the treatment of ovarian cancer. There are multiple routes by which tumor-specific T cell products can be generated. Dendritic cell cancer vaccines can be administered to the patients to induce or bolster T cell responses against tumor antigens or be utilized ex vivo to prime T cells against tumor antigens; these T cells can then be prepared for infusion. ACT protocols can also utilize naturally-occurring tumor-reactive T cells isolated from a patient tumor, known as TILs, as these cells often are heterogeneous in composition and antigen specificity with patient-specific cancer recognition. Alternatively, T cells may be sourced from the peripheral blood, including those that are genetically modified to express a tumor antigen-specific T cell receptor (TCR) or chimeric antigen receptor (CAR) to redirect their specificity and promote their activity against tumor cells expressing the target tumor antigen. Here, we review current ACT strategies for ovarian cancer and provide insights into advancing ACT therapy strategies for the treatment of ovarian cancer.
尽管卵巢癌患者通常对包括化疗和 DNA 修复抑制剂在内的标准治疗方法有反应,但大多数肿瘤仍会复发,这凸显了需要替代疗法。卵巢癌是一种免疫原性癌症,其中肿瘤浸润淋巴细胞(TILs),特别是 T 细胞的积累与患者更好的预后相关。因此,通过被动给予 T 细胞来利用免疫系统,这一过程称为过继细胞疗法(ACT),是治疗卵巢癌的一种很有前途的治疗选择。有多种途径可以生成针对肿瘤的 T 细胞产品。可以向患者施用树突状细胞癌症疫苗,以诱导或增强针对肿瘤抗原的 T 细胞反应,或在体外利用它们来针对肿瘤抗原对 T 细胞进行预刺激;然后可以准备这些 T 细胞进行输注。ACT 方案还可以利用从患者肿瘤中分离出的天然存在的肿瘤反应性 T 细胞,即 TILs,因为这些细胞在组成和抗原特异性方面通常具有异质性,具有针对患者特异性癌症的识别能力。或者,可以从外周血中获取 T 细胞,包括那些经过基因修饰以表达肿瘤抗原特异性 T 细胞受体(TCR)或嵌合抗原受体(CAR)以改变其特异性并促进其对表达靶肿瘤抗原的肿瘤细胞的活性的 T 细胞。在这里,我们综述了当前用于卵巢癌的 ACT 策略,并就如何推进 ACT 治疗策略以治疗卵巢癌提供了一些见解。
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