Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity
| العنوان: | Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity |
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| المؤلفون: | Matthias Gromeier, Jana M. Cable, Smita K. Nair, Michael C. Brown, Mubeen Mosaheb, Yuanfan Yang, David M. Ashley, Elena Y. Dobrikova, Hideho Okada, Darell D. Bigner |
| المصدر: | Nature Communications Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, General Physics and Astronomy, Priming (immunology), CD8-Positive T-Lymphocytes, Inbred C57BL, Mice, 0302 clinical medicine, Cytotoxic T cell, Innate, Tumour virus infections, lcsh:Science, Melanoma, Multidisciplinary, Glioma, Acquired immune system, 3. Good health, Poliovirus, Infectious Diseases, 030220 oncology & carcinogenesis, Interferon Type I, Immunotherapy, Development of treatments and therapeutic interventions, Science, Antigen presentation, Genetic Vectors, Biology, Cancer Vaccines, General Biochemistry, Genetics and Molecular Biology, Article, Viral vector, Vaccine Related, 03 medical and health sciences, Antigen, Immunity, Virology, Animals, Humans, Innate immune system, 5.2 Cellular and gene therapies, Inflammatory and immune system, General Chemistry, Dendritic Cells, Immunity, Innate, CNS cancer, Mice, Inbred C57BL, 030104 developmental biology, Emerging Infectious Diseases, Good Health and Well Being, HEK293 Cells, Hela Cells, Tumour vaccines, lcsh:Q, Immunization, HeLa Cells |
| الوصف: | Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models. Experimental PVSRIPO oncolytic virus therapy of glioblastoma has shown long-term efficacy in a subset of patients. Here the authors engineer the virus to enable incorporation of tumor-specific antigens, and show proof-of-principle evidence that this modification increases anti-tumor immunity and extends survival in mice. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f76b6d6a99329397e4021ab8e842ff9cTest http://europepmc.org/articles/PMC6985231Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f76b6d6a99329397e4021ab8e842ff9c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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