Near-Infrared Photothermal Nano-CAR Immunotherapy mediated by engineered exosomes targeted to pancreatic cancer with mutated KRAS

Project Information

NIR-NanoCAR

Grant agreement ID: 101110299

DOI

10.3030/101110299

Project closed

EC signature date 18 July 2023

Start date 1 January 2024

End date 31 December 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 165 312,96

Coordinated by

UNIVERSIDAD DE GRANADA
Spain

Periodic Reporting for period 1 - NIR-NanoCAR (Near-Infrared Photothermal Nano-CAR Immunotherapy mediated by engineered exosomes targeted to pancreatic cancer with mutated KRAS)

Reporting period: 2024-01-01 to 2025-12-31

Summary of the context and overall objectives of the project

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers and continues to show limited response to current therapeutic approaches, including immunotherapy. Novel therapeutic approaches capable of overcoming tumour immune resistance and improving selective drug delivery are therefore urgently needed.
NIR-NanoCAR aimed to develop an innovative extracellular vesicle-based nanoimmunotherapy strategy combining immune-cell engineering, targeted therapeutic delivery and microenvironment reprogramming. The project explored the generation of engineered extracellular vesicles derived from CAR-engineered immune cells and their potential application as multifunctional carriers for PDAC treatment.
The overall objective was to contribute to next-generation combinatorial immunotherapies and support future therapeutic innovation in PDAC.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the project, the main experimental platforms required for the development of the proposed nanoimmunotherapy were established and optimised. A non-soluble mesothelin-targeted CAR construct incorporating IL-12 secretion capabilities was successfully designed and implemented in immune-cell models, enabling the generation of engineered cellular platforms for extracellular vesicle production.
Methodologies for extracellular vesicle production, purification and characterisation were established and refined through the evaluation of different isolation and engineering approaches. Functional assays and proof-of-concept loading experiments demonstrated the feasibility of using engineered extracellular vesicles as delivery platforms.
In parallel, in vitro and in vivo experimental platforms relevant to PDAC research were developed, including three-dimensional cellular models and orthotopic pancreatic tumour models in mice, which will support full evaluation of the proposed therapeutic strategy beyond the fellowship period.
As an additional research component, complementary molecular analyses were incorporated to identify biological pathways potentially relevant for future combinatorial immunotherapy approaches. These activities contributed to expanding the scientific scope of the project and generating new mechanistic hypotheses for future research activities.
Overall, the project enabled the establishment of robust technological and experimental workflows that provide the basis for continued development of this approach. Further results generated through continuation of these activities will be communicated through future scientific publications.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

NIR-NanoCAR contributed to advancing the application of extracellular vesicle engineering and nanoimmunotherapy approaches in PDAC. The project combined concepts that remain relatively unexplored in this disease setting, including engineered immune-cell-derived extracellular vesicles, targeted delivery and modulation of tumour-immune interactions.
Beyond the specific experimental outcomes, the project generated methodological advances and established experimental platforms that support future development of next-generation immunotherapy approaches. These developments create opportunities for combination strategies designed to overcome mechanisms of tumour immune resistance.
From a broader perspective, PDAC remains associated with limited therapeutic options and high societal burden. Therefore, advances in innovative immunotherapy and nanomedicine approaches may contribute in the future to improving treatment opportunities for patients affected by this disease.
The project also generated new research opportunities beyond the fellowship period and contributed to strengthening scientific capacity, interdisciplinary collaboration and future research in the field of CAR-engineered immune cells and extracellular vesicle-associated therapies.