Tania Jain, MBBS

Myelofibrosis is a clonal myeloid malignancy resulting in marrow fibrosis, splenomegaly, and anemia. Transformation to acute leukemia is inevitable if left untreated. High-risk myelofibrosis and acute leukemia evolving from myelofibrosis remain difficult to treat and median survival for these patients is under 2 years. Allogeneic bone marrow transplantation is the only potential cure but limited by non-relapse mortality and relapse. Hence, there remains a critical need to design novel therapeutic options for myelofibrosis to improve patient outcomes and prevent transformation to acute leukemia. Chimeric antigen receptor (CAR) T-cells have emerged as a promising therapy for diverse malignancies, resulting in long-term remission and even cures. We take a novel approach by targeting SLAMF7 in the tumor microenvironment. In myelofibrosis, neoplastic clones comprised of fibrocytes derived from CD14+ monocytes are essential for pathogenesis of underlying marrow fibrosis. Signaling lymphocyte activation molecular F7 (SLAMF7) is differentially expressed on monocytes in patients with myelofibrosis and on human fibrocytes. We, therefore, hypothesize that targeting SLAMF7 using CAR T cells will restore marrow function by mitigating fibrosis and thus improve outcomes in myelofibrosis. In this study, we will identify the correlation of SLAMF7 expression with the severity of myelofibrosis and then evaluate the safety and efficacy of targeting SLAMF7 in myelofibrosis mouse models.