Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer
Menée auprès de trois cohortes incluant au total 25 patientes atteintes d'un cancer de l'ovaire récidivant, cet essai met en évidence l'intérêt, pour améliorer l'immunité antitumorale liée aux lymphocytes T, d'injections intra-ganglionnaires d'un vaccin personnalisé, à base de cellules dendritiques autologues, en combinaison ou non avec le bévacizumab et le cyclophosphamide
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. 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.