| Literature DB >> 29643231 |
Janos L Tanyi1, Sara Bobisse2, Eran Ophir2, Sandra Tuyaerts2, Annalisa Roberti1, Raphael Genolet2, Petra Baumgartner2, Brian J Stevenson3, Christian Iseli3, Denarda Dangaj2, Brian Czerniecki4, Aikaterini Semilietof2, Julien Racle2,3, Alexandra Michel2, Ioannis Xenarios3, Cheryl Chiang1, Dimitri S Monos5, Drew A Torigian6, Harvey L Nisenbaum6, Olivier Michielin2,3, Carl H June7, Bruce L Levine7, Daniel J Powell1, David Gfeller2,3, Rosemarie Mick8, Urania Dafni9, Vincent Zoete2,3, Alexandre Harari2, George Coukos1,2, Lana E Kandalaft10,2.
Abstract
We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.Entities:
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Year: 2018 PMID: 29643231 DOI: 10.1126/scitranslmed.aao5931
Source DB: PubMed Journal: Sci Transl Med ISSN: 1946-6234 Impact factor: 17.956