Scientific article
English

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

Published inScience translational medicine, vol. 10, no. 436, eaao5931
Publication date2018-04-11
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
Affiliation entities Not a UNIGE publication
Funding
  • National Cancer Institute [P50 CA083638]
  • National Cancer Institute [R21 CA156224]
Citation (ISO format)
TANYI, Janos L et al. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. In: Science translational medicine, 2018, vol. 10, n° 436, p. eaao5931. doi: 10.1126/scitranslmed.aao5931
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Article (Published version)
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Identifiers
Journal ISSN1946-6234
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