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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1427428

Efficacy of Novel Allogeneic Whole Cells Vaccine to treat Colorectal Cancer

Provisionally accepted
George Alzeeb George Alzeeb 1*Corinne Tortorelli Corinne Tortorelli 1Jaqueline Taleb Jaqueline Taleb 2Fanny De Luca Fanny De Luca 3Benoit Berge Benoit Berge 4Chloé Bardet Chloé Bardet 5Emeric Limagne Emeric Limagne 6Marion Brun Marion Brun 1Lionel Chalus Lionel Chalus 1Benoit Pinteur Benoit Pinteur 1Paul Bravetti Paul Bravetti 1Céline GONGORA Céline GONGORA 7Lionel Apetoh Lionel Apetoh 8Francois Ghiringhelli Francois Ghiringhelli 6*
  • 1 Brenus Pharma, Lyon, France
  • 2 Université Claude Bernard Lyon 1, Lyon, Rhône-Alpes, France
  • 3 Bio Elpida, Lyon, France
  • 4 Euraxi, Joué-les-Tours, France
  • 5 Anaquant, Villeurbanne, France
  • 6 Centre Georges François Leclerc, Dijon, Burgundy, France
  • 7 INSERM U1194 Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, Languedoc-Roussillon, France
  • 8 Brown Center for Immunotherapy, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States

The final, formatted version of the article will be published soon.

    Colorectal cancer (CRC) remains a significant global health burden, emphasizing the need for innovative treatment strategies. 95 % of the CRC population are microsatellite stable (MSS), insensitive to classical immunotherapies such as anti-PD-1; on the other hand, responders can become resistant and relapse. Recently, the use of cancer vaccines enhanced the immune response against tumor cells. In this context, we developed a therapeutic vaccine based on Stimulated Tumor Cells (STC) platform technology. This vaccine is composed of selected tumor cell lines stressed and haptenated in vitro to generate a factory of immunogenic cancer-related antigens validated by a proteomic cross analysis with patient's biopsies. This technology allows a multi-specific education of the immune system to target tumor cells harboring resistant clones.Here, we report safety and antitumor efficacy of the murine version of the STC vaccine on CT26 BALB/c CRC syngeneic murine models. We showed that one cell line (1CL)-based STC vaccine suppressed tumor growth and extended survival. In addition, three cell lines (3CL)-based STC vaccine significantly improves these parameters by presenting additional tumor-related antigens inducing a multi-specific anti-tumor immune response. Furthermore, proteomic analyses validated that the 3CL-based STC vaccine represents a wider quality range of tumor-related proteins than the 1CL-based STC vaccine covering key categories of tumor antigens related to tumor plasticity and treatment resistance. We also evaluated the efficacy of STC vaccine in an MC38 anti-PD-1 resistant syngeneic murine model. Vaccination with the 3CL-based STC vaccine significantly improved survival and showed a confirmed complete response with an antitumor activity carried by the increase of CD8+ lymphocyte T cells and M1 macrophage infiltration.These results demonstrate the potential of this technology to produce human vaccines for the treatment of patients with CRC.

    Keywords: cancer vaccine, stimulated tumor cells, colorectal cancer, Antigens, Haptenation, immune response, Proteomics, Immunotherapy

    Received: 03 May 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Alzeeb, Tortorelli, Taleb, De Luca, Berge, Bardet, Limagne, Brun, Chalus, Pinteur, Bravetti, GONGORA, Apetoh and Ghiringhelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    George Alzeeb, Brenus Pharma, Lyon, France
    Francois Ghiringhelli, Centre Georges François Leclerc, Dijon, Burgundy, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.