CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Understanding CAR T cell therapy and its role in ovarian cancer and peritoneal carcinomatosis from ovarian cancer.
Understanding CAR T cell therapy and its role in ovarian cancer and peritoneal carcinomatosis from ovarian cancer.
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卵巢癌是全球女性第七常见癌症,也是致死率最高的妇科恶性肿瘤,原因在于缺乏准确的早期筛查工具且症状出现较晚。由于早期症状缺失,诊断常延迟至疾病进展到晚期,通常已累及腹膜。卵巢癌是异质性恶性肿瘤,组织病理类型各异,但晚期肿瘤治疗通常以化疗和肿瘤细胞减灭术为主。CAR-T 细胞已显示治疗血液系统恶性肿瘤的前景,但其治疗实体瘤的作用尚不明确。由于 CAR-T 细胞向肿瘤部位迁移能力低、肿瘤微环境具有保护作用且肿瘤细胞表面抗原异质,治疗结局较差。尽管疗效存在这些局限,CAR-T 细胞已被提出用于治疗结直肠癌和胃癌来源的腹膜癌病。与全身给药相比,局部腹腔内给予 CAR-T 细胞效果更好,可提高肿瘤缩小程度、延长疗效、预防局部复发和远处转移,并减少全身不良反应。本文综述 CAR-T 细胞治疗卵巢癌及卵巢癌来源腹膜癌病的应用。
Ovarian cancer is the seventh most common cancer worldwide in women and the most lethal gynecologic malignancy due to the lack of accurate screening tools for early detection and late symptom onset. The absence of early-onset symptoms often delays diagnosis until the disease has progressed to advanced stages, frequently when there is peritoneal involvement. Although ovarian cancer is a heterogeneous malignancy with different histopathologic types, treatment for advanced tumors is usually based on chemotherapy and cytoreduction surgery. CAR T cells have shown promise for the treatment of hematological malignancies, though their role in treating solid tumors remains unclear.
Outcomes are less favorable owing to the low capacity of CAR T cells to migrate to the tumor site, the influence of the protective tumor microenvironment, and the heterogeneity of surface antigens on tumor cells. Despite these results, CAR T cells have been proposed as a treatment approach for peritoneal carcinomatosis from colorectal and gastric origin.
Local intraperitoneal administration of CAR T cells has been found to be superior to systemic administration, as this route is associated with increased tumor reduction, a more durable effect, protection against local relapse and distant metastases, and fewer systemic adverse effects. In this article we review the application of CAR T cells for the treatment of ovarian cancer and peritoneal carcinomatosis from ovarian cancer.
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