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Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity

Medicine and Health

Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity

M. M. Mosaheb, E. Y. Dobrikova, et al.

This groundbreaking study by Mubeen M. Mosaheb and colleagues demonstrates the potential of the poliovirus:rhinovirus chimera, PVSRIPO, to enhance antitumor cytotoxic T lymphocyte responses. The research showcases its ability to induce effective immune responses against tumors, marking a significant step in cancer therapy.... show more
Abstract
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.
Publisher
Nature Communications
Published On
Jan 27, 2020
Authors
Mubeen M. Mosaheb, Elena Y. Dobrikova, Michael C. Brown, Yuanfan Yang, Jana Cable, Hideho Okada, Smita K. Nair, Darell D. Bigner, David M. Ashley, Matthias Gromeier
Tags
antitumor
cytotoxic T lymphocytes
poliovirus
genetically stable vectors
tumor growth
dendritic cells
CD8 T cells
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