Maria Grazia Roncarolo

Roncarolo laboratory is exploring the basic biology and translational applications of human type 1 regulatory cells (Tr1). We are using engineered Tr1, ex vivo Tr1, and alloantigen-specific Tr1 to uncover the molecular frameworks that govern Tr1 identity, differentiation and function. We are also translating Tr1 into the clinic. First, Tr1 can be used as a supportive cell therapy to enhance stem cell engraftment and immune reconstitution after hematopoietic stem cell transplantation (HSCT). Alloantigen-specific Tr1, designed to prevent graft-vs-host disease (GvHD) after allogeneic HSCT, are already being tested in a phase I/II clinical trial (NCT03198234). Second, we are investigating the mechanisms of action and clinical potential of the engineered Tr1 called CD4(IL-10) or LV-10, generated by lentiviral transduction of CD4 T cells with IL10 gene. Besides their immunosuppressive and anti-GvHD properties, LV-10 lyse primary acute myeloid leukemia (AML) cells and delay myeloid leukemia progression in vivo. We are exploring LV-10 as a novel cell immunotherapy for AML. Finally, we are interested in curing inborn errors of immunity by stem cell transplantation or autologous stem cell gene correction. We are testing a gene editing strategy to correct pathogenic mutations in IL10 and IL10 receptor genes, which cause severe and debilitating VEO-IBD (very early onset inflammatory bowel disease) in infants and young children.