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

Détails

ID Serval
serval:BIB_CBC10D090AEF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer.
Périodique
Science translational medicine
Auteur(s)
Tanyi J.L., Bobisse S., Ophir E., Tuyaerts S., Roberti A., Genolet R., Baumgartner P., Stevenson B.J., Iseli C., Dangaj D., Czerniecki B., Semilietof A., Racle J., Michel A., Xenarios I., Chiang C., Monos D.S., Torigian D.A., Nisenbaum H.L., Michielin O., June C.H., Levine B.L., Powell D.J., Gfeller D., Mick R., Dafni U., Zoete V., Harari A., Coukos G., Kandalaft L.E.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Statut éditorial
Publié
Date de publication
11/04/2018
Peer-reviewed
Oui
Volume
10
Numéro
436
Pages
NA
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Antigens, Neoplasm/immunology, Bevacizumab/therapeutic use, Cancer Vaccines/therapeutic use, Cyclophosphamide/therapeutic use, Dendritic Cells/metabolism, Female, Humans, Immunotherapy/methods, Mutation/genetics, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/therapy, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/metabolism
Pubmed
Web of science
Création de la notice
19/04/2018 20:10
Dernière modification de la notice
28/09/2019 5:08
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