Development and validation of a novel rationally designed immunotherapeutic combination strategy built upon targeting RANK(L) for cervical cancer. 01/11/2020 - 31/10/2022

Abstract

Cervical cancer (CC) patients, especially those with advanced disease, are urgently in need of new treatment options that can increase their survival rate and quality of life. A promising strategy is immunotherapy, however, only a minority of patients responds to it because the cancer has developed mechanisms that evade its effects. In recent years, the RANKL/RANK signaling pathway has been implicated as one such mechanism, as it allows many cancer types - including CC - to circumvent the immune response by disrupting the communication of the immune cells. Supported by our first results, we strongly believe that blocking the RANKL/RANK signal can release the brakes on the immune system and reinvigorate the tumor's susceptibility to immunotherapy. We therefore aim to expose the best possible immunotherapeutic partner(s) for anti-RANK(L) therapy in order to achieve the most optimal anti-tumor immune effects. For this, we have unique access to CC samples retrieved from patients before and after anti-RANKL monotherapy, which we will thoroughly investigate to reveal immune related changes. Thereafter, we will perform additional laboratory tests that will allow us to pinpoint one best-in-class anti-RANKL combination strategy, which we will further optimize in CC mouse models. Finally, this project will validate a novel imaging technique to stratify patients and monitor treatment response for this therapy, thereby minimizing treatment - and economic burden.

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The development of an off-the-shelf immunological combination therapy for glioblastoma multiforme 01/12/2017 - 31/12/2018

Abstract

We will study the contribution of hypoxia-inducible factors (HIF) to innate immunosuppression in glioblastoma (GBM) in hypoxia. The capacity of HIF inhibitors combined with an immunostimulant to eliminate GBM cells will be studied in hypoxic cocultures of human GBM cells, natural killer cells and macrophages. This study will elucidate mechanisms of GBM-mediated immunosuppression and will generate valuable new insights for the development of novel efficacious immunotherapeutic strategies to treat GBM.

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    Exploring HIF in poly(I:C)-based immunotherapy to stimulate innate immunity in glioblastoma multiforme 01/10/2017 - 30/09/2019

    Abstract

    We will study the contribution of hypoxia-inducible factors (HIF) to innate immunosuppression in glioblastoma (GBM) in hypoxia. The capacity of HIF inhibitors combined with the immunostimulant poly(I:C) to eliminate GBM cells will be studied in hypoxic cocultures of human GBM cells, natural killer cells and macrophages. This study will elucidate mechanisms of GBM-mediated immunosuppression and will generate valuable new insights for the development of novel efficacious immunotherapeutic strategies to treat GBM.

    Researcher(s)

    Research team(s)

    Exploring HIF in poly(I:C)-based immunotherapy to stimulate innate immunity in glioblastoma multiforme. 01/10/2015 - 30/09/2017

    Abstract

    We will study the contribution of hypoxia-inducible factors (HIF) to innate immunosuppression in glioblastoma (GBM) in hypoxia. The capacity of HIF inhibitors combined with the immunostimulant poly(I:C) to eliminate GBM cells will be studied in hypoxic cocultures of human GBM cells, natural killer cells and macrophages. This study will elucidate mechanisms of GBM-mediated immunosuppression and will generate valuable new insights for the development of novel efficacious immunotherapeutic strategies to treat GBM.

    Researcher(s)

    Research team(s)

      Stimulation of the suppressed innate antitumor immunity in glioblastoma. 01/01/2014 - 31/12/2014

      Abstract

      Glioblastoma is the most common, malignant, primary brain tumor. One of the characteristics of this (and other) cancer(s) is suppression of the immune system. The aim of this research is to (re )activate the antitumoral functions of the innate immune cells in glioblastoma. This will be achieved by combining direct stimulation of the innate immune cells with alleviation of the protumoral and immunosuppressive tumor microenvironment.

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