Wood Jana, Yasmin-Karim Sayeda, Mueller Romy, Viswanathan Akila N, Ngwa Wilfred
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 04181 Kosice, Slovakia.
Cancers (Basel). 2020 Apr 22;12(4):1026. doi: 10.3390/cancers12041026.
Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival ( = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.
晚期宫颈癌目前的治疗选择有限，尤其是对于资源匮乏地区的患者，其5年总生存率为17%。在此，我们报告了晚期宫颈癌动物模型的研究结果，表明抗CD40疗法可有效增强远隔效应，即对一个部位的肿瘤进行放射治疗可在远处未治疗部位的肿瘤产生具有治疗意义的反应。在本研究中，在每只动物身上生成了两个皮下宫颈癌肿瘤，分别代表一个原发性肿瘤和一个转移性肿瘤。仅对原发性肿瘤进行治疗，并监测两个肿瘤的反应。根据不同的治疗参数重复该研究，包括放疗剂量和免疫佐剂抗CD40的给药方案。结果一致表明，单次剂量的激动性抗CD40与单次分割剂量的放疗可产生高效的远隔效应，动物存活率显著提高（P = 0.0004）。总体而言，接受该联合治疗的小鼠中有60%显示长期存活且肿瘤完全消退，而其他组小鼠的肿瘤则持续生长。此外，对该治疗有反应的小鼠再次受到攻击后出现白癜风，表明对这种癌症产生了免疫记忆。这些发现提供了一种潜在的新治疗方法，可进一步研究和开发用于治疗晚期宫颈癌，具有重大潜在影响，尤其是在资源匮乏地区。
