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

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.