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卵巢癌的过继性 T 细胞治疗

英文原题:Adoptive T cell therapy for ovarian cancer.

查看英文原题

Adoptive T cell therapy for ovarian cancer.

PubMed 2024/04/10(内容时间) Gynecol Oncol Q1 · IF 4.5(JCR 2025)

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中文摘要

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有应答,但多数肿瘤会复发,凸显替代疗法的必要性。卵巢癌具有免疫原性,TIL(肿瘤浸润淋巴细胞)积聚,尤其是T细胞浸润,与患者结局较好相关。

因此,通过被动输注T细胞来利用免疫系统的过继细胞治疗(ACT),是治疗卵巢癌的一种有前景选择。生成肿瘤特异性T细胞产品有多种途径。可向患者给予树突状细胞癌症疫苗,以诱导或增强针对肿瘤抗原的T细胞应答;也可在体外用疫苗刺激T细胞,再制备细胞用于输注。ACT方案还可使用从患者肿瘤中分离的天然肿瘤反应性T细胞,即TIL;这类细胞组成和抗原特异性通常具有异质性,并能识别患者自身肿瘤。或者,T细胞也可取自外周血,包括经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)的细胞,从而重定向其特异性并增强其对表达靶抗原肿瘤细胞的活性。本文综述卵巢癌当前ACT策略,并为推进卵巢癌ACT治疗提供见解。

展开英文摘要原文

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.

论文信息

作者
Gitto SB、Ihewulezi CJN、Powell DJ Jr
第一作者单位
Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.United States
通讯作者单位
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. Electronic address: poda@pennmedicine.upenn.edu.United States
文献类型
综述 · 美国 NIH 资助研究
期刊
Gynecologic oncology2024 Jul
原文标识
PubMed 38603955 · DOI 10.1016/j.ygyno.2024.04.001