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.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_313F7CD9FDBC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of translational medicine
Author(s)
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. (co-last), Kandalaft L.E.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Publication state
Published
Issued date
26/11/2019
Peer-reviewed
Oui
Volume
17
Number
1
Pages
391
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
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.
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.
Keywords
Cancer immunotherapy, Cyclophosphamide, Dendritic cell vaccine, Neoantigen, Neoepitope, Ovarian cancer
Pubmed
Web of science
Open Access
Yes
Create date
29/11/2019 12:42
Last modification date
11/12/2020 6:26
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