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

Cell Rep Med. 2021-03; 
Weldy V Bonilla, Nicole Kirchhammer, Anna-Friederike Marx, Sandra M Kallert, Magdalena A Krzyzaniak, Min Lu, Stéphanie Darbre, Sarah Schmidt, Josipa Raguz, Ursula Berka, Ilena Vincenti, Mindaugas Pauzuolis, Romy Kerber, Sabine Hoepner, Stephan Günther, Carsten Magnus, Doron Merkler, Klaus K Orlinger, Alfred Zippelius, Daniel D Pinschewer
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ORF cDNA Clones/MolecularCloud … cDNAs encoding for the L and NP ORFs as well as for the full-length L and S segments of CAND and PICV were synthesized by Genscript, the Netherlands, and were ligated into polymerase-II- and polymerase-I-driven expression cassettes, respectively. MOPV cDNAs for virus … Get A Quote

摘要

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 genealogicall... More

关键词

CD8 T cells, Pichinde virus, anti-vector immunity, arenavirus, lymphocytic choriomeningitis virus, pre-existing immunity, therapeutic tumor vaccine, tumor control, viral genealogy