banda transcan 2 2016ul

Title: Dual epigenetic targeting and immunotherapy to fight against cancer


Project Coordinator:
Felipe PROSPER (Spain) Clinica Universidad de Navarra, Pamplona, Navarra


Project Partners:
Karine BRECKPOT (Belgium) Vrije Universiteit Brussel (VUB), Laboratory of Molecular and Cellular Therapy, Laarbeeklaan, Brussels
Anna MONDINO (Italy) San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Milan


Project Abstract:
Background/rationale: Epigenetic modifications are implicated in a variety of diseases including cancer. Thus, its modulation by using inhibitors of DNA methyltransferases (DNMT) or histone deacetylases have been developed and proved efficacious against cancer.
Recent evidence further suggests that these drugs have immunomodulatory properties and synergize with immunotherapy, representing another major breakthrough in cancer therapy. We developed novel compounds that simultaneously inhibit the activity of the histone methyltransferase G9a and DNMT1, showing a potent in vitro and in vivo activity against a wide range of cancers. These inhibitors also promote a pro-inflammatory signature, which might favor anti-tumor immunity.
Hypothesis: Combination of the newly defined epigenetic drugs with immunotherapeutic strategies represents a novel targeted chemo-immunotherapy approach with synergistic effects against cancer.
Aims:
1) To study the molecular events underlying the anti-tumor and immunomodulatory activities of the newly defined G9a/DNMT1 dual inhibitor (CM272) in vitro and in vivo in comparison with approved hypomethylating agents.
2) To develop a novel combinatorial strategy with state-of-the art immunotherapies leading to a first-in-man clinical study.
Methods: Antitumor effect of CM272 will be tested in murine tumor models, alone or combined with vaccines, checkpoint inhibiting antibodies or adoptive T cell therapy. Immune cell subsets (effector T cells, Treg cells, and antigen presenting cells) will be studied over the course of treatment and tumor debulking on sorted populations by gene expression analysis, flow cytometry and functional assays.
Expected results and potential impact: Preclinical data will help elucidate anti-tumor and immunomodulatory effects of the newly designed dual epigenetic drug and define novel combinatorial strategies suitable for clinical application. Efficacy and safety will be determined to design a first-in-man-clinical study.


(Project selected for funding under JTC 2015)


TRANSCAN News

Launch of the call: JTC 2021
The new TRANSCAN-3 project consortium is launching the first Joint Transnational Call for proposals, co-funded by the European Commission, on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment"

International Networking Event (virtual)
on 22 April 2021 hrs 9:00 CET
will focus on the forthcoming co-funded JTC 2021 on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment" 
the event is organized by TUBITAK under the “Turkey in Horizon 2020 Phase II” Technical Assistance Project
in cooperation with TRANSCAN-3

ERA-NET Cofund TRANSCAN-3:
 Sustained collaboration of national and regional programmes in cancer research
is the new project funded by the European Commission under H2020  which started on 1st March 2021 and will last five years (G. A. no. 964264)

A TRANSCAN-2 brochure, highlighting key achievements, is available for download

 

eu flagship

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643638.

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