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- Multidimensional assessment of virus-associated head and neck cancer patients for the discovery of predictive biomarkers to guide clinical intervention
- TArgeting drug resistant melanoma with miCroRNAs delivered by Lipid NanoparTICles (TACTIC)
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- Developing a Biobank Network Among Major Sarcoma Treatment Centers to Improve Biomedical Research
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- Exploring the role of Bcl-2 family in the immune surveillance of melanoma: from mechanisms to therapeutic perspectives
- Exploring how endothelin-1/PIEZO axis intersects mechanical forces to fuel PARP inhibitor resistance in ovarian cancer
TArgeting drug resistant melanoma with miCroRNAs delivered by Lipid NanoparTICles (TACTIC)
Project description
PI: --
Other IRE Principal Collaborators Involved: Donatella Del Bufalo, Luigi Fattore, Marta Di Martile
Project duration: 24 months
Project code: PNRR-POC-2022-12375713
BRAF-mutated metastatic melanoma relapsing after targeted or immunotherapy represents an aggressive disease with significant unmet clinical needs. Current therapeutic options are limited, with standard chemotherapy (dacarbazine) offering a limited life expectancy. This project builds upon a recent discovery and patent from the team (PCT/IT2019/050073) regarding the use of specific oncosuppressor microRNAs (miRNAs), delivered via lipid nanoparticles (LNPs), in combination with targeted therapies to overcome drug resistance in melanoma. Preliminary in vitro and in vivo studies have already demonstrated the antitumor efficacy of this strategy. The project aims to optimize the composition of LNP-miRNAs, complete preclinical efficacy and preliminary toxicology studies, in order to prepare the clinical translation into Phase I-II studies.
Purpose
Establish a reproducible and scalable protocol for the production of LNP-miRNAs.
Fully characterize LNP-miRNA formulations in terms of size, stability, encapsulation efficiency, and toxicity in vitro and in vivo.
Demonstrate the efficacy of LNP-miRNAs in reversing drug resistance in preclinical melanoma models, both in vitro and in vivo, including in combination with targeted therapies.
Assess the preliminary safety of LNP-miRNAs through acute toxicity, maximum tolerated dose, and repeated-dose toxicity studies in murine models.
Analyze the effects of LNP-miRNA treatment on the tumor microenvironment (TME) and immune response in PDX models.
Obtain robust preclinical data to support clinical translation and the application for funding for Phase I-II clinical trials.
Expected Outcomes
Advancement in melanoma management: The project aims to provide a breakthrough in melanoma management, with a combinatorial approach to maximize patient life expectancy and quality of life.
Novel therapeutic strategy for drug resistance: Development of an innovative therapeutic strategy based on LNP-miRNAs to overcome resistance to targeted therapies in patients with BRAF-mutated metastatic melanoma.
Preclinical data to support clinical trials: Obtaining a solid package of preclinical data on the antitumor efficacy and preliminary safety of LNP-miRNAs, necessary to support the transition to Phase I-II clinical trials.
Impact on the healthcare system: Potentially increasing the chances of cure and overcoming drug resistance for melanoma patients, reducing the impact of the disease on the healthcare system.
Funding and industrial partnership prospects: The results of the project can be used to apply for funding dedicated to clinical development and to attract biotech or industrial partners interested in further supporting the program.
Financial Support
PNRR, financed by Ministero della Salute
The total grant of the project is: € 960.000,00
The grant assigned to IFO – IRE is: € 250.000,00
Other Institution involved: Sapienza – University of Rome, Università di Napoli Federico II, IRCCS Istituto Nazionale Tumori Fondazione G. Pascale
The funding resources are from the public notice 2° Avviso pubblico per la presentazione e selezione di progetti di ricerca da finanziare nell’ambito del PNRR sulle seguenti tematiche:
- Proof of concept (PoC);
- Tumori Rari (TR);
- Malattie Rare (MR);
- Malattie Croniche non Trasmissibili (MCnT) ad alto impatto sui sistemi sanitari e socio-assistenziali:
- Innovazione in campo diagnostico,
- Innovazione in campo terapeutico;
- Malattie Croniche non Trasmissibili (MCnT) ad alto impatto sui sistemi sanitari e socio-assistenziali:
- Fattori di rischio e prevenzione,
- Eziopatogenesi e meccanismi di malattia
Piano Nazionale di Ripresa e Resilienza - Missione M6 - Componente C2 - Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN finanziato dall’Unione europea - NextGenerationEU.