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

Project description

Next-generation immunotherapy for pancreatic cancer

KRAS is a key oncogene mutated in many cancers, including pancreatic ductal adenocarcinoma (PDAC). It encodes a small GTPase involved in cell signalling pathways regulating growth, differentiation and survival and thus KRAS mutations cause uncontrolled cell proliferation. Despite its therapeutic potential, targeting KRAS has encountered many challenges. With the support of the Marie Skłodowska-Curie Actions programme, the NIR-NanoCAR project aims to overcome this problem through an innovative approach that combines photothermal therapy and exosomes from CAR T-cells. The idea is to utilise exosomes as vehicles for the delivery of IL-12 and siRNA targeting KRAS in cancer cells. This hybrid nanotherapy will be tested in a murine PDAC model for efficacy.

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.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSIDAD DE GRANADA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 165 312,96
Address
CUESTA DEL HOSPICIO SN
18071 GRANADA
Spain

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Region
Sur Andalucía Granada
Activity type
Higher or Secondary Education Establishments
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Total cost

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