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Open Access 01-12-2019 | Vaccination | Protocol

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

Authors: Apostolos Sarivalasis, Caroline Boudousquié, Klara Balint, Brian J. Stevenson, Philippe O. Gannon, Emanuela Marina Iancu, Laetitia Rossier, Silvia Martin Lluesma, Patrice Mathevet, Christine Sempoux, George Coukos, Urania Dafni, Alexandre Harari, Michal Bassani-Sternberg, Lana E. Kandalaft

Published in: Journal of Translational Medicine | Issue 1/2019

Abstract

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.

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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
Authors: Apostolos Sarivalasis
Caroline Boudousquié
Klara Balint
Brian J. Stevenson
Philippe O. Gannon
Emanuela Marina Iancu
Laetitia Rossier
Silvia Martin Lluesma
Patrice Mathevet
Christine Sempoux
George Coukos
Urania Dafni
Alexandre Harari
Michal Bassani-Sternberg
Lana E. Kandalaft
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Vaccination
Ovarian Cancer
Ovarian Cancer
Published in: Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-019-02133-w

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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

Abstract

Background

Methods

Discussion

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Abstract

Background

Methods

Discussion

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