Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer.
Details
Serval ID
serval:BIB_CBC10D090AEF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer.
Journal
Science translational medicine
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
11/04/2018
Peer-reviewed
Oui
Volume
10
Number
436
Pages
NA
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
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
Create date
19/04/2018 21:10
Last modification date
28/09/2019 6:08