NIR-NanoCAR · Near-Infrared Photothermal Nano-CAR Immunotherapy mediated by engineered exosomes targeted to pancreatic cancer with mutated KRAS
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2024-01-01 → 2025-12-31
- EU contribution
- €165,313
- Participants
- 2
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Near-Infrared Photothermal Nano-CAR Immunotherapy mediated by engineered exosomes targeted to pancreatic cancer with mutated KRAS
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.
Data: CORDIS, © European Union
Project objective
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate under 10%. Current treatments for PDAC are based on ineffective and unspecific drugs that cause hard side effects. Besides, new T cell-based immunotherapies are toxic and unsuccessful in most solid tumors, including PDAC. Activating KRAS mutations occur in almost all patients, but unfortunately, KRAS is difficult to target. This discouraging situation highlights the need to design orthogonal and innovative strategies that target different pro-tumoral axes, in order to increase the antitumor effect minimizing side effects. In NIR-NanoCAR project, we will develop a new concept of therapy, Near-Infrared (NIR) Photothermal Nano-CAR Immunotherapy (NIR-PNCI). To test this concept, we will fuse i) thermosensitive liposomes capable to mediate photothermal therapy by NIR, with ii) exosomes derived from mesothelin-CAR T cells armored with IL-12 (which maintain effector molecules from their parental cells) and loaded with siRNA targeted to mutated KRAS. We will explore the antitumor capability and the tumor microenvironment-reprograming mediated by the hybrid nanotherapy in a relevant murine PDAC model. If successful, this nanosystem will be a breakthrough with a paradigm shift in the strategy to design the next generation of nanoimmunotherapies for solid tumors.
Original text from CORDIS.
Participants
Links
- View on CORDIS
- DOI: 10.3030/101110299
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e510678155&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e52e956e1f&appId=PPGMS
Data: CORDIS, © European Union