Stanley Riddell, M.D.

Clinical Expertise

Dr. Riddell is an expert in using hematopoietic (blood-forming) stem cell transplantation (HCT) to treat patients with leukemias, lymphomas and other blood-related cancers, and in treating graft-versus-host disease (GVHD) that can occur when a donor’s immune T cells attack normal tissues as well as the malignancy. Based on his extensive clinical experience and laboratory investigations, Dr. Riddell has developed innovative therapies that use T cells to treat various viral infections and cancers. He was the principal investigator on the first human trial of transferred therapeutic T cells, to prevent dangerous cytomegalovirus infections after HCT, and on four subsequent clinical trials of ‘adoptive’ T cell therapy, including the first using leukemia-reactive T cells to treat relapsed leukemia post-transplant and the first using CAR-engineered T cells of defined subset composition.

Research Focus

Dr. Riddell’s early studies demonstrated the potential to augment T cell immunity by the adoptive transfer of antigen-specific T cells and uncovered mechanisms by which virally-infected cells evade immune recognition. These findings provided insights into similar mechanisms that tumors use to escape T cell immunity and that might be therapeutically targeted to improve patient outcomes. More recently, the Riddell team identified the subset of T cells that can best survive and function after transfer to patients and found that using clearly defined combinations of T-cell types can make the therapy even more effective. They have developed critical techniques for the isolation, expansion, genetic modification and reinfusion of therapeutic T cells, and for monitoring patient safety as well as T cell persistence, migration and function post-infusion. Many of these powerful methods are now broadly used in developing adoptive immunotherapies, including state-of-the-art ways to identify the tumor antigens recognized by T cells and to rapidly multiply the number of disease-fighting T cells.

Current Laboratory Projects

Dr. Riddell’s research group continues to make new discoveries to enable the development of effective T cell therapies for more patients. They are:

• Detailing the mechanisms involved in the beneficial anti-cancer effects of donor T cells versus their role in potentially dangerous GVHD, and addressing these processes to increase the safety and relapse-preventing efficacy of HCT,
• Using clinical samples and animal models to dissect how cancers can evade T cell immune responses and evaluate strategies to achieve effective antitumor immunity by overcoming immune evasion,
• Identifying tumor antigens that can be recognized by T cells and developing engineered TCRs or CARs using emerging principles of synthetic biology, and
• Elucidating intrinsic T cell properties that are important for effective adoptive T cell therapy, including qualities of particular T cell subsets.