Summary
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.
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101165187 |
| Start date: | 01-01-2025 |
| End date: | 31-12-2029 |
| Total budget - Public funding: | 1 503 155,00 Euro - 1 503 155,00 Euro |
Cordis data
Original description
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.
Status
SIGNEDCall topic
ERC-2024-STGUpdate Date
22-11-2024
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