SPOKE 5
Next-Generation Therapies
Design and validation of innovative, tailored, and personalized therapeutic strategies, including gene and cell therapies, antibody-based drugs, and novel molecules.
Spoke Leader and Expertise
Università degli Studi di Milano-Bicocca
The University of Milano-Bicocca is recognized for its well-established expertise in immunology, experimental pharmacology, and the development of advanced therapies for precision medicine. Within HEAL Italia, Spoke 5 leads the transformation of biological knowledge and predictive models into personalized therapeutic strategies, with a particular focus on cell therapies and new pharmacological approaches based on the molecular mechanisms of disease.
Partners
- IRCCS Centro di Riferimento Oncologico di Aviano
- Istituto Superiore di Sanità
- Istituto di Ricerche Farmacologiche Mario Negri
- IRCCS Neuromed – Istituto Neurologico Mediterraneo
- Opella Healthcare Italy S.r.l.
- Sapienza Università di Roma
- SIT – Sordina IORT Technologies S.p.A.
- Fondazione Toscana Life Sciences
- Alma Mater Studiorum Università di Bologna
- Università degli Studi di Cagliari
- Università degli Studi di Catania
- Università degli Studi di Modena e Reggio Emilia
- Università degli Studi di Palermo
- Università di Pisa
- Università degli Studi di Verona
Scientific Coordinator
Prof.ssa Francesca Granucci
Mission
The mission of the thematic network (Spoke 5) is to develop next-generation therapies and personalized therapeutic strategies, moving beyond a one-size-fits-all approach to treatment in favor of interventions tailored to the biological characteristics of each patient. In precision medicine, therapy is selected based on the molecular mechanisms of the disease and the individual response to treatments.
Objectives
- Develop more effective and safer therapies.
- Personalize treatments based on individual biological profiles.
- Reduce variability in drug response.
- Accelerate the transfer of therapeutic innovations into clinical practice.
Activities
The activities of Spoke 5 cover the entire therapeutic value chain, from design to preclinical validation. A central area focuses on the development of advanced cell therapies, such as CAR-T (Chimeric Antigen Receptor T cells), immune system cells engineered to recognize and destroy specific cancer cells.
Spoke 5 also works on drug repurposing, that is, the use of already approved molecules for new therapeutic indications, reducing development time and costs. Particular attention is given to the use of advanced experimental models, including organoids, to test treatment efficacy in systems that faithfully reproduce patient tissue.
A further area of activity concerns the study of the gut microbiota, the collection of microorganisms that inhabit the intestine, as a modulator of responses to drugs and immunotherapies.
Areas of work
Targeting strategies: innovative approaches for selective and specific therapeutic targeting
- Design, synthesis, and validation of TRID (Translational Readthrough Inducing Drugs) to overcome nonsense mutations
- Identification of correctors of misfolding and post-transcriptional defects of the CFTR protein in Cystic Fibrosis
Innovative Immunotherapies
- Synthesis of antibody-drug conjugates (ADC) for the treatment of selected neoplasms
- Targeting nucleotides, their receptors, and extracellular catabolism to enhance immune response in solid tumors
- Generation and characterization of CAR-modified cells for the treatment of solid tumors and fibrosis
- Development of next-generation immunotherapies for oncological, infectious, and autoimmune diseases
- Induction of immune tolerance through the delivery of autoantigens to the liver for the treatment of autoimmune diseases
Design of targeted microbiota-based interventions tailored to patient, disease, and tissue
- Development of personalized microbial consortia and next-generation microorganisms
- In vivo validation of the therapeutic activity of microbial consortia in patient microbiota “avatars”
Identification of new therapeutic targets through screening and drug repurposing
- Definition of putative therapeutic targets through computational tools and virtual screening of drug libraries
- In vitro validation of the efficacy and selectivity of selected drugs
- Drug repurposing through biobank screening: the NAFLD/NASH GDR case study
- Development and validation of new targeted radionuclides and precision Flash radiotherapy procedures
Projects Funded through Cascade Calls
CAR-MA
Formulation of biomimetic Artificial Nano-Vesicles using Microfluidics technology for the transport and delivery of CAR proteins for innovative Immunotherapy
The research project aims to develop advanced biomimetic nanovesicles, produced through microfluidic technology, for the targeted delivery of chimeric T cell receptors (CAR) against specific proteins expressed in glioblastoma. These nanovesicles, named CAR-MA, will be optimized to engineer healthy lymphocytes, transforming them into cells capable of expressing the desired chimeric receptors through a targeted cell modification process. Through this strategy, CAR-MA lymphocytes will be able to selectively recognize tumor cells, validating the effectiveness of the system and its precision of action in advanced 3D in vitro glioblastoma culture models.
ORGANO-CAR
Development of an ORGANOid-Based Platform for CAR-T Validation UsingNanoparticles Mediated mRNA Delivery
The ORGANO-CAR project aims to improve immunotherapy for solid tumors, where the interaction between the immune system and the tumor microenvironment limits the effectiveness of CAR-T cells. The objective is to develop an integrated platform that combines tumor organoids and nanotechnologies to optimize and validate these therapies. Organoids—three-dimensional models that replicate tumors in vitro—will enable the study and enhancement of the safety, efficacy, and translational potential of CAR-T therapies in solid tumors.
CA.RE.BIOS “Campus Regi Biologia” Srl, Lead Institution
Università degli Studi di Catanzaro “Magna Graecia”
Università degli Studi di Brescia
IRCCS, Centro di Riferimento Oncologico della Basilicata – IRCCS CROB
PROPHECY-GlycoRARE
Predictive Research On Personalized Healthcare through Experimental Characterization of Yielding GLYCOprotein Rare Ailments and Responsive Endoplasmic reticulum modulation for therapeutic handling
The project aims to discover new drug candidates based on protein–protein interaction (PPI) inhibitors, specifically targeting α-Galactosidase A (α-Gal) mutants for precision medicine in Fabry disease. This cutting-edge research lays the methodological foundations for future applications across a wide range of other protein targets, positioning itself as a seminal model in the field of molecular pharmacology.
