Project description
Advancing CAR-T cells engineered in vivo
Chimeric antigen receptors (CAR) T cells are engineered in the lab, usually using viral vectors to express the various parts of the receptor. The ERC-funded INVIVO-CAR-T project proposes an in vivo gene-modification approach using a synthetic adeno-associated virus (AAV) vector with a tropism for T cells. Researchers will undertake extensive profiling of these in vivo-engineered CAR-T cells and evaluate their therapeutic efficacy in mouse models. Additional experiments have been planned to express costimulatory molecules for improved efficacy and adapt these CAR-T cells for therapy against solid tumours. The goal is to improve CAR-T cell engineering towards more potent effector cells that persist in vivo for longer.
Objective
T cells expressing chimeric antigen receptors (CAR) have transformed cell therapies against some hematological cancers. As a postdoc, I evolved a synthetic adeno-associated virus (AAV) with tropism against murine T cells, providing a unique tool to study gene targeted T cells in immunocompetent cancer models. In this proposal, capitalizing on my break-through, I will develop novel strategies to generate gene targeted CAR-T cells in vivo, optimizing AAV delivery in immunocompetent mouse models and combining these methods with technologies for Cas9 delivery for T cell-specific gene editing. The ultimate goal of my proposal is to develop methods that can be translated to clinical trials in humans. Therefore, I will establish a humanized mouse model that allows for targeting of human T cells in vivo, in which key findings from this research project will be translated for proof-of-concept experiments. As the first ever study of gene targeted T cells in vivo, this ground-breaking research will provide in-depth profiling of in vivo engineered CAR-T cells and their therapeutic potential. This study is a necessary first step forwards toward accessible and affordable in vivo generated CAR-T cell therapies in humans.
Furthermore, to extend the use of CAR-T cells against solid tumor, I have developed an AAV-based platform to perform pooled knock-in T cell screens in immunocompetent solid tumor mouse models. For this research proposal, I have designed a library of synthetic costimulatory receptors to be expressed with a CAR at the Trac locus to improve T cell fitness and persistence. By combining advanced T cell engineering with analysis on single-cell level, these pioneering experiments will answer crucial questions for T cell therapies and tumor biology. To succeed with my ambitious and unconventional proposal, I plan to join the Department of Medicine, Huddinge, at the Karolinska Institute. Building a collaborative team in an excellent translational research environment.
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 medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
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-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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-STG
See all projects funded under this callHost institution
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.
171 77 STOCKHOLM
Sweden
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.