Immunology of organ transplant and cell therapy (CAR) - Research unit

The Cell Factory research interests focus on the pre-clinical and clinical development of advanced therapy medicinal products (ATMP). For the past two decades, the unit has pioneered the use of cell therapy for viral infections in solid organ and stem cell transplantation (HSCT), and in hematology and oncology. The current research activity is directed to the cure of polyomavirus-associated progressive multifocal leukoencephalopathy, and the development of cell therapy programs based on the use of banked multivirus-specific T-cells.
Regarding the hematology/oncology setting, the unit participates in a phase I/II study to prevent leukemia relapse in children given haploidentical HSCT through the administration of donor-derived leukemia blast-stimulated T cells, and is implementing protocols to expand leukemia neoantigen-specific T cells, chimeric antigen receptor (CAR)-modified T cells, and NK cells for clinical application. Finally, the group is developing immune-modulating and regenerative medicine programs based on the use of mesenchymal stromal cells or their acellular derivatives.

• Comoli P., Basso S., Riva G., Barozzi P., Guido I., Gurrado A., Quartuccio G., Rubert L., Lagreca I., Vallerini D., Forghieri F., Morselli M., Bresciani P., Cuoghi A., Paolini A., Colaci E., Marasca R., Cuneo A., Iughetti L., Trenti T., Narni F., Foà R., Zecca M., Luppi M., Potenza L. BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors. Blood, 2017;
• Berzero G., Basso S., Stoppini L., Palermo A., Pichiecchio A., Paoletti M., Lucev F., Gerevini S., Rossi A., Vegezzi E., Diamanti L., Bini P., Gastaldi M., Delbue S., Perotti C., Seminari E., Faraci M., Luppi M., Baldanti F., Zecca M., Marchioni E., Comoli P. Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy. Annals of Neurology, 2021;
• Comoli P., Basso S., Zecca M., Pagliara D., Baldanti F., Bernardo M.E., Barberi W., Moretta A., Labirio M., Paulli M., Furione M., Maccario R., Locatelli F. Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. American Journal of Transplantation, 2007;
• Comoli P., Pedrazzoli P., Maccario R., Basso S., Carminati O., Labirio M., Schiavo R., Secondino S., Frasson C., Perotti C., Moroni M., Locatelli F., Siena S. Cell therapy of stage IV nasopharyngeal carcinoma with autologous EBV-targeted cytotoxic T-lymphocytes. Journal of Clinical Oncology, 2005;
• Comoli P., Labirio M., Basso S., Baldanti F., Grossi P., Furione M., Viganò M., Fiocchi R., Rossi G., Ginevri F., Gridelli B., Moretta A., Montagna D., Locatelli F., Gerna G., Maccario R. Infusion of autologous EBV-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood, 2002.

GMP Facility for cell and gene therapy production; R&D labs equipped to perform flow-cytometry, cell sorting, and functional immunology testing, including a fluorescence ELISPOT reader for cytokine production analysis, a Perkin Elmer beta and gamma counter for cytotoxicity and proliferation assay read-out, and a Nanosight for nanoparticle analysis. The lab is also equipped for quantitative PCR technology.

Lombardy Region, Cellular platforms for the research & development of Advanced Therapy Medicinal products, FORCE-4-CURE; Lombardy Region Foundation for Research (FRRB): Una rete per terapie geniche e cellulari per malattie devastanti (Plagencell); Ministry of Health (Ricerca Finalizzata): T cell therapy for polyomavirus JC-related progressive multifocal leukoencephalopathy; Ministry of Health (Ricerca Corrente): Advanced therapy medicinal product based on mutated nucleophosmin (NPM)1-specific cytotoxic T cells for treatment of patients with relapsed/refractory NPM1-mutated acute myeloid leukemia.

Ospedale Pediatrico Bambino Gesù (F Locatelli, C Quintarelli) for cell and gene therapy; Hematology Dept, Modena and Reggio Emilia University (M Luppi) for leukemia immune response and cell therapy, and for pathogen immunity; Transplantation and Clinical Virology, University of Basel (Prof. HH Hirsch) for polyomavirus immunity and cell therapy; Cellular Therapy & Immunobiology Working Party (CTIWP) of the European Group for Blood and Marrow Transplantation.