Experts call them ‘living drugs’, they are not molecules synthesized in the laboratory, but cells of the immune system, T lymphocytes, which researchers are capable of ‘training’ and arming against tumors through genetic engineering techniques. A ‘revolution’ that of Car-T therapies is taking shape and boasts growing numbers: to date there are already 6 approved drugs and more than 1,400 clinical trials registered worldwide. The prospects of this therapeutic route were taken stock today in Milan where over a thousand scientists gathered to discuss the new frontiers of immunotherapy at Cicon23 (International Cancer Immunotherapy Conference), an event organized by the Italian Network for biotherapy and immunotherapy of tumors (Nibit), ongoing until tomorrow, Saturday 23 September.
The conference offers an insight into the academic and industrial realities involved in the development of new therapies of this type. “Our immune system – explains Anna Mondino, head of the Lymphocyte Activation Unit at the Irccs San Raffaele hospital in Milan – has evolved to learn to recognize infectious agents such as viruses and bacteria, and is capable of recognizing even ‘crazed tumor cells’ ‘ and often to eliminate them before a real tumor even develops. In some cases, however, the tumor hides itself or switches off the immune responses, escaping control and taking over. Hence the idea of trying to amplify the mechanisms natural cells of the immune system”.
To date, adds Giulia Casorati, head of the Experimental Immunology Unit at San Raffaele, “anti-tumor lymphocytes can be obtained directly from patients’ tumors (lymphocytes infiltrating tumors), or generated in the laboratory through genetic engineering. In fact, we have learned to genetically modify cells of the patient’s immune system with natural molecules (such as the T cell receptor, Tcr), or synthetic ones (such as the chimeric antigen receptor, Car) that guide them to recognize and kill tumor cells”. A strategy studied by Chiara Bonini, now full professor of Hematology at Vita-Salute San Raffaele University, who as a student in the group directed by Claudio Bordignon published the first work on the genetic engineering of lymphocytes in 1997 in ‘Science’.
“Today we know how to turn on and off molecules that can respectively activate or inhibit lymphocytes – explains Bonini – and we have new, increasingly effective and safe methodologies for genetically modifying patients’ cells. The results are exciting. Car-T therapy has achieved a complete response in a high percentage of patients in the treatment of some hematological malignancies. However, we know that patients can have clinical relapses because the tumor learns to escape therapy.”
Furthermore, the treatment of solid tumors represents additional obstacles. “We are providing Car-Ts with new weapons against neuroblastoma, a disease currently without a real therapeutic alternative”, comments Gianpietro Dotti, an Italian researcher now at the Lineberger Comprehensive Cancer Center at the University of North Carolina in the United States. Among the speakers at Cicon23 there will also be Cassian Yee from the University of Texas, among the first to have created a genetic map of anti-tumor lymphocytes, recently published in the journal ‘Nature Medicine’.
“We have a critical mass of cutting-edge clinicians and researchers, hospital reference centers of excellence, a prepared regulatory agency, and the support of important funding agencies such as the Italian Association for Cancer Research – concludes Pier Francesco Ferrucci, president of Nibit and director of the Tumor Biotherapy Unit at the European Institute of Oncology (Ieo) in Milan – Cellular therapy can be used in combination with traditional therapies such as chemotherapy and radiotherapy, and also with new strategies such as mRNA vaccines, and immune checkpoint inhibitors. The time has come to network the skills present in the area and work together to make these therapies an effective clinical reality. This is one of the aims of Nibit”.
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