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DART

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Driving tumour antigen presentation by RNA-mediated transdifferentiation

Immunotherapy has transformed cancer treatment, but targeting effectively refractory solid tumors remains a challenge due to poor T cell activation. Downregulation of antigen presentation pathways and lack of professional antigen... ver más

31/01/2026

LUNDS UNIVERSITET

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LUNDS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-08-01

ERC-2024-POC: ERC PROOF OF CONCEPT GRANTS Objective:ObjectivesThe ERC Proof of Concept Grants aim at facilitating exploration of the commercia...

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Duración del proyecto: 17 meses Fecha Inicio: 2024-08-01
Fecha Fin: 2026-01-31

Líder del proyecto

LUNDS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Immunotherapy has transformed cancer treatment, but targeting effectively refractory solid tumors remains a challenge due to poor T cell activation. Downregulation of antigen presentation pathways and lack of professional antigen presenting cells in the tumor microenvironment contribute to immune evasion. My group has demonstrated direct reprogramming of fibroblasts or tumor cells into type 1 conventional dendritic cells (cDC1) cells by overexpression of the transcription factors PU.1, IRF8, and BATF3, moving towards clinical application via a viral gene therapy. Despite its potential for first-in-class therapy, viral approaches still face limitations including inefficient targeting of solid tumors in vivo and challenging scalability.The DART project builds on the ERC-funded project TrojanDC and aims to develop in vivo reprogramming of tumor cells into cDC1-like cells using RNA vectors. I will firstly evaluate the capacity of modified linear, self-replicating, and circular RNA encoding the factors to reprogram fibroblasts in vitro and assess their antigen presentation and cytokine secretion function. Secondly, I will evaluate RNA-mediated reprogramming of cancer cells and assess anti-tumor immunity in vivo as monotherapy and in combination with immune checkpoint blockade. The goal is to optimize RNA vector designs for the most effective in vivo reprogramming considering differences in delivery efficiency, expression kinetics and immunogenicity. Collaborations with clinicians and industry partners like Asgard Therapeutics are integral, ensuring commercialization through novel intellectual property, broad dissemination, and product development.DART will enable RNA-mediated induction of antigen-presenting phenotypes in cancer cells, leading to potent and specific immunity towards tumor-specific antigens. DART will result in an off-the-shelf, safe, and scalable immunotherapy solution that also has the potential to enhance current immunotherapy approaches.

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