作者: George Coukos , Urania Dafni , Alexandre Harari , Michal Bassani‑Sternberg , Lana E Kandalaft
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摘要: Background Most ovarian cancer patients are diagnosed at a late stage with 85% of them relapsing after surgery and standard chemotherapy; for this reason, new treatments are urgently needed. Ovarian cancer has become a candidate for immunotherapy by reason of their expression of shared tumor‑associated antigens (TAAs) and private mutated neo‑antigens (NeoAgs) and the recognition of the tumor by the immune system. Additionally, the presence of intraepithelial tumor infiltrating lymphocytes (TILs) is associated with improved progression‑free and overall survival of patients with ovarian cancer. The aim of active immunotherapy, including vaccination, is to generate a new anti‑tumor response and amplify an existing immune response. Recently developed NeoAgs‑based cancer vaccines have the advantage of being more tumor specific, reducing the potential for immunological tolerance, and inducing robust immunogenicity. Methods We propose a randomized phase I/II study in patients with advanced ovarian cancer to compare the immunogenicity and to assess safety and feasibility of two personalized DC vaccines. After standard of care surgery and chemotherapy, patients will receive either a novel vaccine consisting of autologous DCs pulsed with up to ten peptides (PEP‑DC), selected using an agnostic, yet personalized, epitope discovery algorithm, or a sequential combi‑nation of a DC vaccine loaded with autologous oxidized tumor lysate (OC‑DC) prior to an equivalent PEP‑DC vaccine. All vaccines will be administered in combination with low‑dose cyclophosphamide. This study is the first attempt to compare the two approaches …