Research ArticleCancer

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

See allHide authors and affiliations

Science Translational Medicine  11 Apr 2018:
Vol. 10, Issue 436, eaao5931
DOI: 10.1126/scitranslmed.aao5931

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

The personalized touch in cancer vaccination

Transfer of autologous dendritic cells (DCs) has been investigated as a method of boosting T cell responses in therapeutic vaccines for several diseases. Tanyi et al. report the findings of a clinical study involving recurrent ovarian cancer patients. Patient DCs were pulsed with oxidized tumor lysate before transfer and given alone or in combination with immunomodulatory drugs. The DC vaccine was well tolerated and induced potent antitumor T cell responses, including to new epitopes, that correlated with better prognosis. These results suggest further testing of this vaccination regimen for inducing protective T cell immunity in cancer.

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.

View Full Text