Fatemeh Sobhanimonfared1, Taravat Bamdad2, Zohreh Azita Sadigh3, Hamzeh Choobin4. 1. Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: malihehsobhani@gmail.com. 2. Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Bamdad_T@modares.ac.ir. 3. Human Viral Vaccine Department, Razi Vaccine and Serum Research Institute, Karaj, Iran. Electronic address: z.sadigh@rvsri.ir. 4. Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: h.chubin13@gmail.com.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULT: The results showed increased efficacy of virotherapy in combination with immune-stimulators and tumor cells injection in tolerant mice compared to normal mice. CONCLUSION: Specific tolerance against the oncolytic virus enhances the efficacy of virotherapy both in monotherapy and in combination with immunotherapy.
BACKGROUND: 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. MATERIALS AND METHODS: For tolerance induction, the newborn mice were injected with vesicular stomatitis virus (VSV) subcutaneously. After injection of TC-1tumor 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. RESULT: The results showed increased efficacy of virotherapy in combination with immune-stimulators and tumor cells injection in tolerant mice compared to normal mice. CONCLUSION: Specific tolerance against the oncolytic virus enhances the efficacy of virotherapy both in monotherapy and in combination with immunotherapy.
Authors: Yang Gao; Yan Wu; Tian Huan; Xiaoyan Wang; Jun Xu; Qinggang Xu; Feng Yu; Haifeng Shi Journal: Biotechnol Lett Date: 2021-08-26 Impact factor: 2.461
Authors: Dong Ho Shin; Teresa Nguyen; Bulent Ozpolat; Frederick Lang; Marta Alonso; Candelaria Gomez-Manzano; Juan Fueyo Journal: J Immunother Cancer Date: 2021-04 Impact factor: 12.469