Bone Marrow Grafting and Cellular Therapy for Leukemia and Lymphoma

Project Summary/Abstract: Hematopoietic cell transplantation (HCT) and cellular therapies are effective treatments for a broad range of hematological malignances, representing the first successful and widely applied cellular therapy for cancer. In this revised Program Project Grant competitive renewal (years 34-38), we will probe the cellular basis of transplantation biology (Project 1 and 3) and cell therapies with novel cellular populations, including iNKT cells (Project 1), CAR T cells (Projects 2 and 3), Treg cells (Project 2) and novel antibody constructs (Project 4). The overall goals of our Program Project Grant are to develop a more robust fundamental understanding of transplantation biology and cellular therapies and to address the major challenges of HCT including reducing transplantation risks, preventing graft-vs-host-disease (GvHD) and disease relapse. We will utilize innovative animal modeling, comprehensive biological and molecular analysis, novel imaging and biologically focused translational clinical trials. Our Program involves four highly interactive Projects focusing on: addressing transplantation risk (Projects 3 and 4), the biology and prevention of GVHD (Projects 1, 2 and 3), prevention and treatment of disease relapse with iNKT cells (Project 1), CAR T cells (Project 2 and 3) and targeted immunotherapy strategies focused on the stem cell antigen CD117 (Project 4). These Projects are supported by 3 Cores (Administration, Biostatistics and Data Management and Correlative Sciences). Through our highly interactive Program Project, we will gain novel insights into the biology of HCT and cellular therapies and develop innovative strategies to improve outcomes for patients with hematological malignancies. The knowledge gained has profound implications for extending these therapies to other cancers and for the treatment of patients with a broad range of immunological conditions such as autoimmune disorders and organ transplantation.