Project description
New immunotherapies for cancer and beyond
Chimeric antigen receptor (CAR) T cells are genetically engineered immune cells that destroy target cells with precision thanks to combined antigen binding and T cell activating functions. Their adaptation has enabled new treatments in patients with haematological B cell malignancies. They are very promising for other cancer types and diseases, such as senescence-associated pathologies, but limitations from the antigenic heterogeneity or impaired T cell trafficking must be solved. The EU-funded CARsen project will develop a novel therapeutic concept through the engineering of T cells against senescent cells that will be combined with therapies that induce senescence in tumour cells. The new therapy will be tested for safety and efficacy in murine models of cellular senescence and solid tumours.
Objective
The adoptive transfer of T cells expressing CD19-directed chimeric antigen receptors (CARs) has yielded remarkable efficacy in patients with hematological B-cell malignancies. CARs are a class of synthetic receptors that reprogram T cell specificity, function and metabolism. Engineered T cells are applicable in principle to other cancers and diseases, but clinical success will critically depend on further progress to overcome current limitations such as antigenic heterogeneity or impaired T cell trafficking and function. We propose to develop CAR T cells targeting senescent cells as a novel therapeutic concept for cancer and senescence-associated diseases. Cellular senescence is a stress-response program characterized by stable cell cycle arrest that serves as a potent tumor-suppressive mechanism. Conversely, accumulation of senescent cells generates a chronic inflammatory milieu, which contributes to a plethora of pathologies, such as liver or lung fibrosis and can even promote tumor progression.
Our preliminary data demonstrate that CAR T cells can efficiently clear senescent cells, providing therapeutic benefit in a murine model of liver fibrosis. We thus firmly believe that senolytic CAR T cells have broad therapeutic potential. To this end, we will apply innovative engineering strategies to develop modular CAR designs tailored to senescence-specific requirements. We will determine safety and efficacy of senolytic CAR T cells in murine models of cellular senescence and solid tumors. Importantly, we will evaluate combined treatment approaches of senescence-inducing therapies with CAR T cells targeting senescent and proliferating tumor cells. Finally, we will investigate engineering tools to optimally direct senolytic CAR activity to mediate durable tumor regression.
This project combines two emerging concepts of anticancer therapies and goes beyond current applications of CAR therapies. The efforts may lead to promising new therapeutic avenues.
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.
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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
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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.
ERC-STG - Starting Grant
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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-2020-STG
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72074 Tuebingen
Germany
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