Περίληψη:
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. Copyright © 2018, American Association for the Advancement of Science.
Συγγραφείς:
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.
Powel, D.J., Jr.
Gfeller, D.
Mick, R.
Dafni, U.
Zoete, V.
Harari, A.
Coukos, G.
Kandalaft, L.E.
Λέξεις-κλειδιά:
autologous oxidized whole tumor cell lysate pulsed dendritic cell vaccine; bevacizumab; cyclophosphamide; dendritic cell vaccine; tumor antigen; unclassified drug; bevacizumab; cancer vaccine; cyclophosphamide; tumor antigen, adult; aged; Article; cancer growth; cancer immunization; cancer survival; CD8+ T lymphocyte; cellular immunity; clinical article; controlled clinical trial; controlled study; drug efficacy; drug manufacture; drug safety; female; human; low drug dose; monotherapy; ovary carcinoma; phase 1 clinical trial; pilot study; priority journal; somatic mutation; unspecified side effect; cytotoxic T lymphocyte; dendritic cell; genetics; immunology; immunotherapy; metabolism; mutation; ovary tumor; procedures, Antigens, Neoplasm; Bevacizumab; Cancer Vaccines; Cyclophosphamide; Dendritic Cells; Female; Humans; Immunotherapy; Mutation; Ovarian Neoplasms; T-Lymphocytes, Cytotoxic
