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Targeting bicarbonate transport as a “first-in-class” therapeutic strategy to promote CD8+ T cell fitness and enhance cancer immunotherapy

Project description

Modification of the tumour microenvironment to improve the efficacy of immunotherapy

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent and aggressive cancer of the pancreas accounting for more than 90 % of all cases, with a 5-year survival rate of less than 8 %. These tumours are characterised by an acidic microenvironment that excludes cytotoxic CD8+ T cells. The EU-funded BasicFit project focuses on the improvement of PDAC treatment using early delivery of lead compounds to improve immunotherapy. The project is based on previously collected data showing that inhibition of a bicarbonate transporter in cancer cells mitigates the acidity of the tumour microenvironment, increasing the fitness of CD8+ T cells. The project study may result in the development of more effective immunotherapeutic regimens in pancreatic cancer treatment.

Objective

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancer types. It is virtually resistant to any sort of therapy, including the most recent immunotherapies. These tumors are characterized by a strong hypoxic, nutrient poor, and acidic tumor microenvironment (TME), in which cytotoxic CD8+ T cells are excluded or absent. In the context of tumor acidity, the role of bicarbonate transporters, key regulators of pH homeostasis, has mostly been neglected so far. Supported by the ERC consolidator grant ImmunoFit, we recently unveiled that the metabolic editing of the TME via inhibition of a specific bicarbonate transporter in cancer cells represent a novel robust therapeutic strategy to mitigate the acidity of the TME, increase the fitness of CD8+ T cells, and render more effective the current immunotherapeutic regimens in pancreatic cancer. To progress on the path from ground-breaking research towards innovation we now propose to de-risk the target by delivering early lead compounds (i.e. blockers) with proven therapeutic efficacy and synergism with immunotherapies in several preclinical tumor models, to be valorized for add-on cancer therapy through follow-up R&D collaborations and/or licensing agreements with Pharmaceutical & Biotech companies. This will lead to the commercialization of our sciences and broad societal impact with the deliverable of a brand-new therapeutic approach and combination regimens which are urgently required to tackle tumor resistance or refractoriness vis-à-vis immunotherapies.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC1

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Host institution

VIB VZW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

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Beneficiaries (1)

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