Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Human Viral Vaccine Department, Razi Vaccine and Serum Research Institute, Karaj, Iran.
Microb Pathog. 2020 Mar;140:103957. doi: 10.1016/j.micpath.2019.103957. Epub 2019 Dec 28.
Activation of the immune system to fight cancer is a major goal in immunology and oncology. Although cancer treatment using oncolytic viruses shows promising results, virus mediated oncolysis induces a weak anti-tumor immune response. Upon application of viruses, immune responses against the virus play a significant role in limiting tumor virotherapy. Although suppression of host immunity increases the efficacy of virotherapy against the tumor, but inhibits anti-tumor immune responses. Induction of viral specific tolerance before viral replication may cause the virus to efficiently replicate in tumor cells without affecting the immune responses against tumor antigens. Investigation of the combined strategy of virotherapy and immunotherapy using irradiated tumor cells along with IL-2 and interferon-alpha in virus specific tolerant mice was the goal of this study.
For tolerance induction, the newborn mice were injected with vesicular stomatitis virus (VSV) subcutaneously. After injection of TC-1 tumor cells to adult tolerant mice and formation of a tumor, irradiated TC-1 cells along with IL-2 and Interferon-alpha expression plasmid were injected twice in mice and followed by virotherapy. Size of tumors and CTL activity against the virus and tumor cells were measured.
The results showed increased efficacy of virotherapy in combination with immune-stimulators and tumor cells injection in tolerant mice compared to normal mice.
Specific tolerance against the oncolytic virus enhances the efficacy of virotherapy both in monotherapy and in combination with immunotherapy.
激活免疫系统来对抗癌症是免疫学和肿瘤学的主要目标。虽然使用溶瘤病毒进行癌症治疗显示出有希望的结果，但病毒介导的溶瘤作用会引起较弱的抗肿瘤免疫反应。在应用病毒时，针对病毒的免疫反应在限制肿瘤病毒疗法方面起着重要作用。尽管抑制宿主免疫会增加病毒疗法对肿瘤的疗效，但会抑制抗肿瘤免疫反应。在病毒复制之前诱导病毒特异性耐受可能导致病毒在肿瘤细胞中高效复制，而不影响针对肿瘤抗原的免疫反应。本研究旨在探讨使用辐照肿瘤细胞与 IL-2 和干扰素-α联合进行病毒特异性耐受小鼠的病毒治疗和免疫治疗的联合策略。
为了诱导耐受，新生小鼠通过皮下注射水疱性口炎病毒（VSV）。在成年耐受小鼠中注射 TC-1 肿瘤细胞并形成肿瘤后，将辐照 TC-1 细胞与 IL-2 和干扰素-α表达质粒两次注射到小鼠中，然后进行病毒治疗。测量肿瘤的大小和针对病毒和肿瘤细胞的 CTL 活性。
结果表明，与正常小鼠相比，在免疫刺激剂和肿瘤细胞注射联合治疗时，溶瘤病毒治疗的疗效增加。
针对溶瘤病毒的特异性耐受增强了病毒治疗的疗效，无论是单独治疗还是与免疫治疗联合治疗。
