Τίτλος:
A Phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) in patients with advanced high-grade ovarian serous carcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 neoantigens (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 combination 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 and to use NeoAgs-based vaccines in ovarian cancer in the adjuvant setting. Discussion: The proposed treatment takes advantage of the beneficial effects of pre-treatment with OC-DC prior to PEP-DC vaccination, prompting immune response induction against a wide range of patient-specific antigens, and amplification of pre-existing NeoAgs-specific T cell clones. Trial registration This trial is already approved by Swissmedic (Ref.: 2019TpP1004) and will be registered at http://www.clinicaltrials.gov before enrollment opens. © 2019 The Author(s).
Συγγραφείς:
Sarivalasis, A.
Boudousquié, C.
Balint, K.
Stevenson, B.J.
Gannon, P.O.
Iancu, E.M.
Rossier, L.
Martin Lluesma, S.
Mathevet, P.
Sempoux, C.
Coukos, G.
Dafni, U.
Harari, A.
Bassani-Sternberg, M.
Kandalaft, L.E.
Περιοδικό:
Journal of Translational Medicine
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
cancer vaccine; cyclophosphamide; dendritic cell vaccine; neoantigen; oxidized tumor cell pulsed dendritic cell vaccine; personalized peptide pulsed dendritic cell vaccine; tumor antigen; unclassified drug; cancer vaccine; peptide, adult; advanced cancer; antineoplastic activity; Article; cancer growth; clinical article; cohort analysis; controlled study; disease free survival; drug safety; feasibility study; female; health care quality; human; human tissue; immune response; immunogenicity; immunological tolerance; immunotherapy; low drug dose; multiple cycle treatment; ovary carcinoma; overall survival; phase 1 clinical trial; phase 2 clinical trial; randomized controlled trial; T lymphocyte; autotransplantation; cancer grading; cancer staging; comparative study; dendritic cell; immunology; neoplasm; ovary tumor; pathology; phase 1 clinical trial (topic); phase 2 clinical trial (topic), Cancer Vaccines; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dendritic Cells; Female; Humans; Neoplasm Grading; Neoplasm Staging; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Peptides; Transplantation, Autologous
DOI:
10.1186/s12967-019-02133-w
