SubsidieMeestersRNA-based cancer ImmunotheraPeutics to Enhance CROssPrimming
The RIPECROP project aims to enhance cancer immunotherapy by developing mRNA-based agents that boost cDC1 cells in tumors to improve anti-tumor T-cell crosspriming.
Projectdetails
Introduction
Cancer immunotherapy achieves unprecedented efficacy against a number of malignant diseases. Preclinical experiments in mouse models conclude that type-1 dendritic cells (cDC1) that present tumor antigens are an absolute requirement for most immunotherapy strategies to be efficacious, including those routinely applied to cancer patients at present.
Role of cDC1 Cells
cDC1 cells are specialized in redirecting engulfed cell-associated antigens to the class I MHC antigen-presentation pathway in the context of IL-12 production and co-stimulation, at least when cDC1 cells are in the presence of moieties denoting viral infection. Such phenomena are key to prime anti-tumor T lymphocytes through a mechanism known as crosspriming.
RIPECROP Project Overview
The RIPECROP project will test immunotherapy agents that enhance the numbers and performance of cDC1 in the tumor tissue microenvironment. The strategies will be based on mRNA constructs that will encode:
- Engineered forms of the cDC1 growth factor sFLT-3L
- Single-chain interleukin-12
- cDC1 specific chemoattractants
- Bispecific costimulatory ligands targeted to surface proteins of cDC1 cells
Therapeutic Agents
The new therapeutic agents in the form of coding mRNAs will be expressed in vivo either intratumorally or using the mRNA-transferred liver as an internal “biofactory” to systemically produce the encoded proteins and their combinations.
Innovative Screening Methods
Innovative in-vivo screenings based on hydrodynamic gene transfer of the liver with various expression plasmids encoding heterodimerization systems will be performed to identify suitable new mRNA-based immunotherapeutic chimeric constructs to enhance antitumor T-cell crosspriming.
Conclusion
Overall, a novel mRNA-based toolbox will be studied both in terms of anti-tumor efficacy and regarding the mechanisms of action, in such a manner that crosspriming will become exploitable in combinatorial approaches for cancer immunotherapy.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.500.000 |
| Totale projectbegroting | € 2.500.000 |
Tijdlijn
| Startdatum | 1-10-2024 |
| Einddatum | 30-9-2029 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMApenvoerder
- UNIVERSIDAD DE NAVARRA
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Driving tumour antigen presentation by RNA-mediated transdifferentiationDART aims to develop RNA-mediated reprogramming of tumor cells into antigen-presenting cells to enhance anti-tumor immunity and create a scalable immunotherapy solution. | ERC Proof of... | € 150.000 | 2024 | Details |
Polyclonal anti-tumor immunity by engineered human T cellsThis project aims to enhance adoptive T cell therapies for solid tumors by engineering TCR sensitivity and safety, creating robust, antigen-agnostic immune responses to improve patient outcomes. | ERC Starting... | € 1.812.500 | 2022 | Details |
Developing the next generation of cis-targeting macrophage-T cell cancer immunotherapiesThis project aims to develop dual-modulatory agents to enhance anti-tumor immune responses in cancer immunotherapy while minimizing side effects, seeking proof-of-concept validation. | ERC Proof of... | € 150.000 | 2023 | Details |
Modular Targeted Nanoplatform for Immune Cell Regulation and TherapyImmuNovation aims to develop a targeted nano-immunoModulator nanovaccine to enhance antitumor immunity against CEACAM5+ gastrointestinal cancers, offering a safer and more effective treatment alternative. | ERC Proof of... | € 150.000 | 2023 | Details |
Engineering B cells to fight cancerThis project aims to develop a novel cancer immunotherapy using engineered B cells to enhance anti-tumor responses through targeted gene integration and localized immune activation. | ERC Consolid... | € 1.996.250 | 2022 | Details |
Driving tumour antigen presentation by RNA-mediated transdifferentiation
DART aims to develop RNA-mediated reprogramming of tumor cells into antigen-presenting cells to enhance anti-tumor immunity and create a scalable immunotherapy solution.
Polyclonal anti-tumor immunity by engineered human T cells
This project aims to enhance adoptive T cell therapies for solid tumors by engineering TCR sensitivity and safety, creating robust, antigen-agnostic immune responses to improve patient outcomes.
Developing the next generation of cis-targeting macrophage-T cell cancer immunotherapies
This project aims to develop dual-modulatory agents to enhance anti-tumor immune responses in cancer immunotherapy while minimizing side effects, seeking proof-of-concept validation.
Modular Targeted Nanoplatform for Immune Cell Regulation and Therapy
ImmuNovation aims to develop a targeted nano-immunoModulator nanovaccine to enhance antitumor immunity against CEACAM5+ gastrointestinal cancers, offering a safer and more effective treatment alternative.
Engineering B cells to fight cancer
This project aims to develop a novel cancer immunotherapy using engineered B cells to enhance anti-tumor responses through targeted gene integration and localized immune activation.
Vergelijkbare projecten uit andere regelingen
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Functional chemical reprogramming of cancer cells to induce antitumor immunityThe RESYNC consortium aims to revolutionize cancer immunotherapy by reprogramming cancer cells into antigen-presenting dendritic cells using small molecules for personalized and safer treatments. | EIC Pathfinder | € 2.966.695 | 2024 | Details |
Breakthrough Neoantigen-specific Tumor-Infiltrating Lymphocyte Therapies Through Novel Dendritic Cell ReprogrammingThe Repro-TIL project aims to enhance tumor-reactive TIL expansion for more effective immunotherapy in solid tumors, paving the way for improved treatment outcomes and commercialization. | EIC Transition | € 2.480.367 | 2025 | Details |
CAR T cells Rewired to prevent EXhaustion in the tumour microenvironmentCAR T-REX aims to enhance CAR T cell efficacy against solid tumors by integrating auto-regulated genetic circuits to prevent exhaustion, using advanced gene editing and delivery technologies. | EIC Pathfinder | € 2.733.931 | 2023 | Details |
Novel peptide-based therapeutics for reprogramming the tumour stroma extracellular matrix using molecular modelling and computational engineeringThe project aims to develop TAX2, a novel peptide therapy targeting the tumor microenvironment to inhibit solid tumor progression and enhance immunotherapy efficacy, with a focus on ovarian cancer. | EIC Accelerator | € 2.434.790 | 2025 | Details |
Functional chemical reprogramming of cancer cells to induce antitumor immunity
The RESYNC consortium aims to revolutionize cancer immunotherapy by reprogramming cancer cells into antigen-presenting dendritic cells using small molecules for personalized and safer treatments.
Breakthrough Neoantigen-specific Tumor-Infiltrating Lymphocyte Therapies Through Novel Dendritic Cell Reprogramming
The Repro-TIL project aims to enhance tumor-reactive TIL expansion for more effective immunotherapy in solid tumors, paving the way for improved treatment outcomes and commercialization.
CAR T cells Rewired to prevent EXhaustion in the tumour microenvironment
CAR T-REX aims to enhance CAR T cell efficacy against solid tumors by integrating auto-regulated genetic circuits to prevent exhaustion, using advanced gene editing and delivery technologies.
Novel peptide-based therapeutics for reprogramming the tumour stroma extracellular matrix using molecular modelling and computational engineering
The project aims to develop TAX2, a novel peptide therapy targeting the tumor microenvironment to inhibit solid tumor progression and enhance immunotherapy efficacy, with a focus on ovarian cancer.