Project description
CAR-T therapy through gut microbiome research
The battle against relapsed or refractory B cell malignancies and myeloma is being transformed by CAR-T cell therapy, a treatment that supercharges the immune system to target cancer. However, this approach faces significant hurdles: its long-term efficacy often diminishes, it can lead to serious toxicities, and it lacks the personalised strategies needed to maximise patient outcomes. A new frontier in addressing these challenges lies in the gut microbiome’s role in boosting CAR-T therapy. In this context, the ERC-funded PowerMiT project aims to uncover how gut and tumour microbiomes, their metabolites, and targeted interventions can enhance CAR-T efficacy, paving the way for safer, more effective cancer immunotherapies tailored to individual needs.
Objective
T cell therapy with chimeric antigen receptor (CAR)-T cells is a curative-intent, transformative treatment aimed to boost antitumor abilities of host T cells against refractory/relapsed B cell malignancies and, recently, against refractory/relapsed myeloma. Major challenges of current CAR-T cell immunotherapies are the loss of long-term efficacy, the occurrence of toxicities including infections, and a lack of personalized patient strategies including biomarkers for response prediction and interventions to enhance CAR-T cell efficacy. This proposal builds on our first evidence for a major role of the gut microbiome in CAR-T cell therapy, and addresses these challenges by presenting a translational research strategy aimed to dissect and leverage the impact of gut microbes in its antitumor efficacy.
In Aim 1, we will investigate the hypothesis that gut and intratumoral microbiome configurations and its metabolites are associated with clinical response of CD19-CAR-T cells in lymphoma, with immunophenotypes of these engineered T cells and the tumor immune microenvironment. We will examine the effects of nutrition and antimicrobial drugs on microbiome features to identify potential mechanisms and therapeutic levers. In Aim 2, we will address the biology of microbiome-CAR-T cell interactions through experimental gut microbiome modulations, and humanizing mice with patient-derived microbial ecologies and individual species and strains in preclinical research models. In Aim 3, we will assess potential therapeutic interventions to increase CAR-T efficacy by investigating the action of microbiome-derived metabolites on CAR-T cells and studying phage- and diet-based interventions to mitigate antibiotic-induced gut microbiome dysbiosis.
Characterising the function of the microbiome and its products in CAR-T immunotherapy harbours an enormous potential to improve current and future T cell transfer therapies for numerous patients suffering from cancer.
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.
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.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences ecology
- medical and health sciences health sciences nutrition
- medical and health sciences basic medicine immunology immunotherapy
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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.1.1 - European Research Council (ERC)
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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.
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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-ERC - HORIZON ERC Grants
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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) ERC-2023-COG
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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.
72074 Tuebingen
Germany
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