Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack

Article Article scientifique Article Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack eng 2021 author Bonilla Weldy V author Kirchhammer Nicole author Marx Anna-Friederike author Kallert Sandra M author Krzyzaniak Magdalena A author Lu Min author Darbre Stéphanie 540647 author Schmidt Sarah author Raguz Josipa author Berka Ursula author Vincenti Ilena 692782 author Pauzuolis Mindaugas 884449 author Kerber Romy author Hoepner Sabine author Günther Stephan author Magnus Carsten author Merkler Doron 735735 author Orlinger Klaus K author Zippelius Alfred author Pinschewer Daniel D 100209 10.1016/j.xcrm.2021.100209 33763654 2666-3791 Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8+ T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. This CTL attack eliminates established solid tumors in a significant proportion of animals, accompanied by protection against tumor rechallenge. The magnitude of CTL responses is alarmin driven and requires combining two genealogically distantly related arenaviruses. Vector-neutralizing antibodies do not inhibit booster immunizations by the same vector or by closely related vectors. Rather, CTL immunodominance hierarchies favor vector backbone-targeted responses at the expense of self-reactive CTLs. These findings establish an arenavirus-based immunotherapy regimen that allows reshuffling of immunodominance hierarchies and breaking self-directed tolerance for efficient tumor control. Dewey 616.07 Swiss National Science Foundation Compartmentalized T cell memory in brain viral infection and autoimmunity 310030_173010 CH Project funding 137 Département de pathologie et immunologie 21F false 565 La Sclérose en plaques 908 Cell Reports. Medicine 2 3 fd30d87d-bf18-48d9-bafa-103e9801a8d7 Article (Published version) Public heterologuearenavirus.pdf 6163398 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack	Cell Reports. Medicine			2021	246	260

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Pauzuolis, Mindaugas