Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Synthetic Chimeric Antigen Receptors: Hijacking Nitrenium Ions for Targeting, Therapy and Safety of Next Generation T Cell Therapy

Project description

Synthetic CAR T platform for effective cancer treatment

CAR T cell therapy shows promise as a cancer treatment, involving the genetic modification of T cells to target cancer cells. However, this therapy can lead to severe side effects and offers limited effectiveness. Researchers are seeking to enhance CAR T cell function, but existing off-the-shelf approaches with complete control over CAR T effector function incur high manufacturing costs. The ERC-funded SynCAR-Ts project aims to create a universal synthetic CAR T cell platform. This platform features an adaptable antigen receptor regulated by synthetic, functionalised targeting ligands. Leveraging highly reactive aryl nitrenium ions, the project will modify proteins, deliver drugs, and develop therapeutics. The goal is to broaden the CAR T targeting spectrum to encompass solid tumours and beyond.

Objective

Chimeric antigen receptor (CAR) T cell therapy is a promising approach for cancer treatment with remarkable clinical outcomes. CAR T therapy involves the isolation of patients T cells that are genetically modified with an engineered antigen receptor to attack cancer cells.
Despite the great promise, the rapid activation and proliferation of CAR T cells can lead to serious side effects. In addition, CAR T therapy is challenged by limited effectiveness, difficulties in infiltrating solid tumors, targeting of healthy cells, cell exhaustion and an expensive, lengthy and personalized manufacturing process. Over the past years, researchers have explored many strategies to improve and control CAR T cell function and to develop more universal CAR T cell platforms. Yet, an off-the-shelf approach that allows full control of CAR T effector function, that is flexible in use and can be obtained at low manufacturing costs, is currently not available.
To address above challenges, I will develop a highly innovative, universal synthetic CAR (SynCAR) T cell platform where the antigen receptor is easily adaptable by using synthetic, functionalized targeting ligands to control T cell effector function in space and time.
At the basis of this proposal lies the use of highly reactive and activatable aryl nitrenium ions for protein modification, drug delivery and as novel class of therapeutics. I will 1) tune nitrenium ion reactivity for bioconjugation and drug activation 2) use enzyme-activatable nitrenium ion precursors for synthetically modified antigen receptors, 3) develop novel nitrenium ion-based prodrug strategies to improve CAR T efficiency and 4) use innovative bioorthogonal chemistry to control CAR T activity in time and space.
In this work, I will develop beyond the state-of-the-art chemical biology methods and molecular targeting tools to control, potentiate, and tune T cell activity with the ultimate goal to broaden the CAR T targeting landscape to solid tumors and beyond.

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.

You need to log in or register to use this function

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

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.

HORIZON-ERC - HORIZON ERC Grants

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-COG

See all projects funded under this call

Host institution

UNIVERSITEIT LEIDEN
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.

€ 2 501 154,00
Address
RAPENBURG 70
2311 EZ Leiden
Netherlands

See on map

Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 501 154,00

Beneficiaries (1)

My booklet 0 0