Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
BMC Cancer. 2019 Mar 6;19(1):203. doi: 10.1186/s12885-019-5415-9.
Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas.
嵌合抗原受体 T（CAR-T）细胞是一种有前途的治疗复发或难治性血液系统恶性肿瘤（包括淋巴瘤）的新方法。鉴于针对 CD19 的 CAR-T 细胞的成功，正在开发和测试新的靶点，因为并非所有的淋巴瘤都表达 CD19。CD30 是一个很有前途的靶点，因为它几乎在所有经典霍奇金淋巴瘤、间变大细胞淋巴瘤和一部分其他淋巴瘤类型（包括皮肤 T 细胞淋巴瘤和弥漫性大 B 细胞淋巴瘤）中都普遍表达。CD30 定向 CAR-T 细胞的临床前研究支持了这种方法的可行性。最近，报道了两项 CD30 定向 CAR-T 细胞治疗复发/难治性 CD30+淋巴瘤（包括霍奇金淋巴瘤）的临床试验，毒性极小，部分患者初步疗效可见。然而，提高 CAR-T 细胞的持久性和扩增是进一步提高这种治疗方法疗效的关键。未来的方向包括优化淋巴细胞耗竭方案、增强向肿瘤部位的迁移，以及与其他免疫调节剂联合应用。预计正在进行和即将进行的几项 CD30 定向 CAR-T 细胞临床试验将进一步增强这种方法，以治疗复发和难治性 CD30+淋巴瘤患者。
