The Stem Cell Transplantation and Cellular Therapy (SCTCT) Program focuses on hematopoietic stem cell transplantation (HSCT), cell-mediated immune therapy, and therapy involving stem cells and mesenchymal stromal cells (MSCs). The program has 80 members (38 primary, 40 associate, 2 adjunct) from 25 departments. The program leader is Dr. Richard Champlin, an accomplished clinical and translational investigator, and co- leaders are Dr. Katayoun Rezvani, an expert in cellular therapy, and Dr. Elizabeth Shpall, a leader in stem cells, cord blood transplantation, and regenerative medicine. The program's goal is to advance and optimize the use of HSCT and cellular therapy for treatment of cancer through translational research bridging stem cell biology, hematopoiesis, transplant/tumor immunology, and regenerative medicine. The program has 4 specific aims that address 4 themes:
Aim 1) to improve the clinical outcomes of hematopoietic transplantation;
Aim 2) to improve supportive care, particularly to prevent infections and graft-vs-host disease, and also to prevent cytokine release syndrome seen with cellular immune therapy;
Aim 3) to develop effective cellular immunotherapy involving antigen-specific T cells and NK cells;
and Aim 4) to define basic biologic mechanisms of normal and malignant stem cells and to develop stem cell and MSC-based therapies for tissue regeneration. Annual direct peer-reviewed funding totals $9.9M, of which $2.4M (24%) is from NCI grants, including 1 P01 and 1 U01. Since the last competitive renewal, total annual direct peer-reviewed funding has increased by 19%. MD Anderson maintains the largest hematopoietic transplantation program in the nation. Since the last submission, the program has published 726 articles: 381 (52%) represent intra-programmatic collaborations, 304 (42%) represent inter-programmatic collaborations, and 444 (61%) include external collaborations. Publications have appeared in high-impact journals including N Engl J Med and J Clin Invest. Forty-one percent of publications have appeared in journals with IF >5, and 15% have been in journals with IF >10. Program members have utilized all 14 Shared Resources. Achievements include developing novel approaches for haploidentical and cord blood transplants; establishing the efficacy of letermovir to prevent CMV infections after HSCT; developing a GMP-compliant ex vivo expansion system for NK cells and producing chimeric antigen receptor (CAR) NK cells, which augment antitumor cytotoxicity, and taking these into phase I/II clinical trials; development of novel technology for manufacturing CAR T cells; leading the multicenter study leading to FDA approval of axicabtagene ciloleucel CAR T cell therapy for lymphoma; identification of novel target antigens for immunotherapy; development of a novel monoclonal antibody and CAR T cell that targets aberrantly expressed leukemia antigen PR1; selection and expansion of endogenous antitumor T cells; and demonstration that ex vivo fucosylation accelerates engraftment of cord blood transplants. These accomplishments are extensions of concepts and preclinical studies by program investigators.
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