Project description
Targeted immunotherapy that simultaneously inhibits immunosuppression
Prostate cancer, the most common cancer in men, responds poorly to immunotherapy. An overexpressed antigen on prostate cancer tumours is the target of choice. Persistent activation of the unfolded protein response (UPR), a driver of immunosuppression, enables tumour cells to evade current immunotherapies. Messenger RNA (mRNA) technology allows strong activation of anti-tumour immune responses and precise, dynamic modulation of the tumour microenvironment. With the support of the Marie Skłodowska-Curie Actions programme, the IMMSTRESS project aims to leverage this combination to deliver targeted immunotherapy while inhibiting two specific branches of the UPR. The goal is to redirect and amplify anti-tumour T cell activity and persistence, potentially opening the door to a general strategy for solid tumours.
Objective
Prostate cancer (PCa) is the most common cancer in men and a leading cause of cancer-related death. Its poor response to current immunotherapies highlights the urgent need for new strategies. Six-Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is a cell-surface antigen overexpressed in most primary and advanced stage PCa, making it a highly attractive immunotherapy target. However, the highly suppressive tumor microenvironment (TME) in PCa strongly limits immunotherapy effectiveness. One of the key drivers of this immunosuppression is the persistent activation of endoplasmic reticulum stress pathways, particularly the inositol-requiring protein 1α (IRE1α) and PKR-like ER kinase (PERK) branches of the unfolded protein response (UPR), which enable tumor cells to survive and evade immune attack. Combining STEAP1-targeted immunotherapies with selective UPR inhibition therefore holds strong potential to overcome these barriers. Due to its transient yet versatile nature, messenger RNA (mRNA) technology enables precise and dynamic modulation of the TME while potently activating anti-tumor immune responses. In this project, we will leverage mRNA platforms to deliver STEAP1-targeted immunotherapies together with UPR inhibition to reprogram the TME for more durable tumor control. Specifically, we will test whether inhibiting IRE1α or PERK can reprogram the PCa TME and unlock the full potential of STEAP1-targeted treatments. By integrating mRNA-based delivery with UPR blockade, we aim to both redirect and amplify anti-tumor T-cell activity while enhancing their persistence in the hostile TME. This approach combines antigen-specific targeting with dynamic immune modulation to overcome immune evasion, achieve durable tumor control, and establish a broadly applicable strategy for solid tumors beyond PCa.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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69120 Heidelberg
Germany
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