Rajendran Sakthi, Li Yating, Ngoh Evelyn, Wong Hiu Yi, Cheng Man Si, Wang Cheng-I, Schwarz Herbert
Department of Physiology, National University of Singapore, Singapore, Singapore.
NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore.
Front Oncol. 2019 Sep 24;9:945. doi: 10.3389/fonc.2019.00945. eCollection 2019.
Hodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and CD137 are expressed on Hodgkin and Reed Sternberg (HRS) cells, the malignant cells in HL. We found that this co-expression is specific for HRS cells. Based on this discovery we developed a bispecific antibody that binds preferentially to the CD30, CD137-double positive HRS cells. The CD30, CD137 bispecific antibody gets internalized into HRS cells opening up the possibility to use it as a carrier for a toxin. This antibody also induces antibody-dependent, cell-mediated cytotoxicity in CD30, CD137-double positive HRS cells. The enhances specificity of the CD30, CD137 bispecific antibody to HRS cells makes it a promising candidate for development as a novel HL treatment.
霍奇金淋巴瘤（HL）是一种常影响年轻成年人的恶性肿瘤。尽管有有效的治疗方法，但并非每个患者都有反应，因此需要开发新的治疗方法，特别是针对复发和难治性病例。两种肿瘤坏死因子受体家族成员CD30和CD137在HL中的恶性细胞霍奇金和里德·斯腾伯格（HRS）细胞上表达。我们发现这种共表达是HRS细胞特有的。基于这一发现，我们开发了一种双特异性抗体，它优先结合CD30、CD137双阳性的HRS细胞。CD30、CD137双特异性抗体被内化到HRS细胞中，从而有可能将其用作毒素载体。该抗体还可在CD30、CD137双阳性的HRS细胞中诱导抗体依赖性细胞介导的细胞毒性。CD30、CD137双特异性抗体对HRS细胞增强的特异性使其成为一种有前景的新型HL治疗候选药物。
