Shenzhen key laboratory of stem cell research and clinical transformation, Guangdong Engineering Technology Research Center of Stem cell and Cell therapy, Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.
Int J Med Sci. 2021 Jul 31;18(15):3380-3388. doi: 10.7150/ijms.61681. eCollection 2021.
Lung cancer remains a global challenge due to high morbidity and mortality rates and poor response to treatment, and there are still no effective strategies to solve it. The bispecific antibody (BsAb) is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. In this study, we combined two BsAbs to achieve a dual-target therapy strategy of EpCAM and MUC-1 with high affinity and specificity. The results showed that the combination of two BsAbs against EpCAM and MUC-1 could inhibit the growth of lung cancer more effectively in cell lines and primary tumors. The superior antitumor effect of two BsAbs could be attributable to enhanced CTL and increased production of type I IFNs. At the same time, the combination of EpCAM/CD3 BsAb and MUC-1/CD3 BsAb significantly regulated T population in the TDLNs. Therefore, we have found a potential immunotherapeutic strategy, which was the combination therapy with EpCAM/CD3 BsAb and MUC-1/CD3 BsAb for the treatment of non-small cell lung cancer.
由于高发病率和死亡率以及对治疗的反应不佳，肺癌仍然是一个全球性的挑战，目前仍然没有有效的策略来解决它。双特异性抗体（BsAb）是一种新型抗体，它可以靶向两个不同的抗原，并通过选择性地将效应细胞重定向到靶细胞来介导特异性杀伤作用。在这项研究中，我们结合了两种 BsAbs，以实现对 EpCAM 和 MUC-1 的高亲和力和特异性的双靶治疗策略。结果表明，两种针对 EpCAM 和 MUC-1 的 BsAbs 的组合可以更有效地抑制细胞系和原发性肿瘤中肺癌的生长。两种 BsAbs 的优越抗肿瘤作用可能归因于增强的 CTL 和增加的 I 型 IFNs 的产生。同时，EpCAM/CD3 BsAb 和 MUC-1/CD3 BsAb 的组合显著调节了 TDLNs 中的 T 细胞群体。因此，我们发现了一种潜在的免疫治疗策略，即 EpCAM/CD3 BsAb 和 MUC-1/CD3 BsAb 的联合治疗用于治疗非小细胞肺癌。
