TY - JOUR
TI - Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer
AU - Tanyi, J.L.
AU - Bobisse, S.
AU - Ophir, E.
AU - Tuyaerts, S.
AU - Roberti, A.
AU - Genolet, R.
AU - Baumgartner, P.
AU - Stevenson, B.J.
AU - Iseli, C.
AU - Dangaj, D.
AU - Czerniecki, B.
AU - Semilietof, A.
AU - Racle, J.
AU - Michel, A.
AU - Xenarios, I.
AU - Chiang, C.
AU - Monos, D.S.
AU - Torigian, D.A.
AU - Nisenbaum, H.L.
AU - Michielin, O.
AU - June, C.H.
AU - Levine, B.L.
AU - Powel, D.J., Jr.
AU - Gfeller, D.
AU - Mick, R.
AU - Dafni, U.
AU - Zoete, V.
AU - Harari, A.
AU - Coukos, G.
AU - Kandalaft, L.E.
JO - Science Translational Medicine
PY - 2018
VL - 10
TODO - 436
SP - null
PB - American Association for the Advancement of Science
SN - 1946-6234, 1946-6242
TODO - 10.1126/scitranslmed.aao5931
TODO - autologous oxidized whole tumor cell lysate pulsed dendritic cell vaccine;  bevacizumab;  cyclophosphamide;  dendritic cell vaccine;  tumor antigen;  unclassified drug;  bevacizumab;  cancer vaccine;  cyclophosphamide;  tumor antigen, adult;  aged;  Article;  cancer growth;  cancer immunization;  cancer survival;  CD8+ T lymphocyte;  cellular immunity;  clinical article;  controlled clinical trial;  controlled study;  drug efficacy;  drug manufacture;  drug safety;  female;  human;  low drug dose;  monotherapy;  ovary carcinoma;  phase 1 clinical trial;  pilot study;  priority journal;  somatic mutation;  unspecified side effect;  cytotoxic T lymphocyte;  dendritic cell;  genetics;  immunology;  immunotherapy;  metabolism;  mutation;  ovary tumor;  procedures, Antigens, Neoplasm;  Bevacizumab;  Cancer Vaccines;  Cyclophosphamide;  Dendritic Cells;  Female;  Humans;  Immunotherapy;  Mutation;  Ovarian Neoplasms;  T-Lymphocytes, Cytotoxic
TODO - 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. Copyright © 2018, American Association for the Advancement of Science.
ER -