Research project on CAR-T cells for hematological malignancies and solid tumors
Funding: The Ministry of Health has funded this research project with a 10.000.000,00 euros grant.The first annual tranche, provided on 19 December 2019 to ACC, amounts to 5.000.000,00 euros.
Abstract: The development of genetically modified T lymphocytes redirected to the tumor target through the expression on the cell surface of a Chimeric Antigen Receptor (CAR), has been a true revolution in the field of immunotherapy for the treatment of Acute Lymphoblastic Leukemia (ALL). Unfortunately, despite significant efficacy, CAR-T cells have been associated with a suboptimal safety profile, since severe, sometimes life-threatening or even fatal toxicities have been reported in patients with B-cell neoplasms given CAR-T cells. Moreover, the clinical outcome of the few patients with solid tumors or hematological malignancies other than B-lymphoproliferative disorders has been less encouraging. For this reason, the CAR-T research project aims to improve the effectiveness of CAR-T cell therapy, through the creation of a collaborative network joining the expertise of the different participating Institutions. The project is articulated on 6 different Work Packages (WP), each with well-defined objectives.
WP1: Coordination; development of an automatic production chain for CAR-T cells and of novel approaches for manufacturing CAR cells immediately available and/or less costly.
WP2: Identification of new targets selectively expressed on neoplastic cells and compatible with the clinical use of CAR-T.
WP3: Preclinical development of CAR-killer cells against novel cancer targets, both in solid tumors and hematologic diseases other than B-cell neoplasms.
WP4: Novel strategies to increase activation, expansion, survival, tissue penetration, cytotoxicity and monitoring of CAR expressing cells.
WP5: Strategies to improve the safety profile of CAR-T cells.
WP6: Legal aspects and intellectual property.
Project coordinator: The scientific coordination was assigned to Prof. Franco Locatelli, Director of the Department of Oncohematology and Cellular Therapy and Genetics of the Ospedale Pediatrico Bambino Gesù.
Partecipating institutions: Ospedale Pediatrico Bambino Gesù IRCCS – Roma, Fondazione Policlinico Universitario Agostino Gemelli IRCCS – Roma, Istituto Europeo di Oncologia S.r.l. – Milano, Fondazione Piemonte per l’Oncologia – Candiolo, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST IRCCS – Meldola, Ospedale San Raffaele S.r.l. – Milano, Fondazione IRCCS Istituto Nazionale Tumori – Milano, Istituti Fisioterapici Ospitalieri – IRCCS – Istituto Nazionale Tumori Regina Elena – Roma, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale” – Napoli, IRCCS Centro di Riferimento Oncologico della Basilicata – Rionero in Vulture, Istituto Tumori “Giovanni Paolo II”, IRCCS – Bari, Istituto Clinico Humanitas – Humanitas Mirasole S.p.A. – Rozzano, Istituto Oncologico Veneto IRCCS – Padova, Centro di Riferimento Oncologico di Aviano IRCCS – Aviano, Fondazione di Religione e di Culto “Casa Sollievo della Sofferenza” Opera di San Pio da Pietrelcina – San Giovanni Rotondo, Ospedale S. Gerardo – Fondazione Tettamanti – Monza, MolMed S.p.a., Istituto di Biostrutture e Bioimmagini del CNR – Napoli.
Starting and ending date:The project started on November 27th 2019 and it will end on November 26th 2021