Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer

Author: Tanyi, Janos L.; Bobisse, Sara; Ophir, Eran; Tuyaerts, Sandra; Roberti, Annalisa; Genolet, Raphael; Baumgartner, Petra; Stevenson, Brian J.; Iseli, Christian; Dangaj, Denarda; Czerniecki, Brian; Semilietof, Aikaterini; Racle, Julien; Michel, Alexandra; Xenarios, Ioannis; Chiang, Cheryl; Monos, Dimitri S.; Torigian, Drew A.; Nisenbaum, Harvey L.; Michielin, Olivier; June, Carl H.; Levine, Bruce L.; Powell, Daniel J.; Gfeller, David; Mick, Rosemarie; Dafni, Urania; Zoete, Vincent; Harari, Alexandre; Coukos, George; Kandalaft, Lana E.

Description: 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-naive, 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.

Subject headings: Antigens; Neoplasm; Bevacizumab; Cancer Vaccines; Cyclophosphamide; Dendritic Cells; Female; Humans; Immunotherapy; Mutation; Ovarian Neoplasms; T-Lymphocytes; Cytotoxic

Publication year: 2018

Journal or book title: Science Translational Medicine

Volume: 10

Issue: 436

Pages: eaao5931

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Serial number: 3698

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