"Treating cancer with oncolytic viruses delivered in mesenchymal cells"
Manuel Ramirez Orellana
Hospital Infantil Universitario Niño Jesús
Lunes 20 de Diciembre de 2020, 11:00, Salón de grados Edificio Politécnico
Oncolytic Viruses (OVs)s are natural or modified viruses that infect tumor cells, kill them and enhance an antitumor immune through response against OV-mediated immunogenic tumor cell death. Repeated systemic administration for metastatic tumors this is hampered by immune-mediated clearance or neutralization of the virus and limited by toxicity. We have developed Celyvir, the combination of bone marrow-derived mesenchymal cells carrying an OV. The use of MSCs as OVs’ carriers theoretically offers various advantages: targeted delivery of the OV to the tumor sites and protection from the immune blockade. To date, Celyvir development program has completed a first Phase I trial for children and adults, and a compassionate use program, in which 30 additional patients, mostly pediatric, have been treated. Extensive studies of patients treated with Celyvir and several animal models allowed us to confirm the capacity of MSCs to home into tumor metastases, locally delivering their viral cargos. In addition, we have found that higher MSC permissiveness to viral replication and lower innate response of MSCs to adenoviral infection are major determinants of clinical outcome. These “immunologically silent” MSCs will not activate the immune system prematurely after IV inoculation, allowing a better tumor homing and, at the same time, a better replication of the viruses inside the MSCs.