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Engineering the immunosuppressive microenvironment in mesothelioma with targeted LipidNanoParticles encapsulating self-amplifying RNA

Project description

Innovative immunotherapy for the treatment of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a highly aggressive disease and standard chemotherapy treatment achieves an overall survival of 12 months. Anti–programmed cell death 1 protein immunotherapy has a low response rate and does not improve the patient's survival due to the immunosuppressive tumour microenvironment. The EU-funded OncoNanoR project aims to develop innovative immunotherapy for the treatment of MPM, involving activation of the innate and adaptive tumour microenvironment. The goal is to achieve an intracellular delivery of self-amplifying RNA using intravenous injection of MPM-targeted lipid nanoparticles.

Objective

Malignant pleural mesothelioma (MPM) is a highly aggressive disease, where chemotherapy remains the standard of care, enabling an overall survival (OS) of 12 months. Anti-PD-1-based immunotherapy has not improved the patient's OS, while providing only a response rate of 21%, owing to the immunosuppressive tumor microenvironment.
The originality of this proposal relies on engineering a novel form of immunotherapy for the treatment of MPM, through activating the innate and adaptive tumor microenvironment, upon one single intravenous injection of self-amplifying RNA, intracellularly delivered by a targeted LipidNanoparticle, which has recently proven to successful target small drugs to orthotopic MPM.
This proposal challenges a major dogma in onconanomedicine targeting nucleic acids to extra-hepatic tumors - where I will have the guidance of Prof. Moreira from CNC, UC, who holds more than 25 years of experience in the field of targeted delivery to solid tumors, being a successful entrepreneur. Supervision will be complemented with the guidance of an immunologist (APaiva), clinical pathologist (ACarmo), expert on physical-chemistry of colloids (BSilva) and drug development (Srgio Simes, supervisor at Bluepharma Pharmaceutical Industry).
This Marie Sklodowska-Curie European Fellowship, in line with Europe Mission on Cancer, is a life time opportunity to gain a number of different transferable skills, mentoring and leadership, networking and knowledge dissemination, exploitation and communication. These will enable me to become a highly qualified researcher, able to generate and integrate differentiated and interdisciplinary knowledge, and with know-how on how to translate it towards the market and the patients. As such, a wide avenue of opportunities will be open to further pursue a career either in Academia as Principal Investigator/Group Leader or Senior Scientist in the R&D department of a company dedicated to cancer immunotherapies and/or complexes injectables.

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Coordinator

UNIVERSIDADE DE COIMBRA
Net EU contribution
€ 215 773,20
Address
PACO DAS ESCOLAS
3004-531 Coimbra
Portugal

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Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)