Stanley R.

Riddell

M.D.

Research and/or clinical interests 

Dr. Stan Riddell is a world leader in developing immunotherapies, which harness the power of the immune system to fight cancers and dangerous infections. His research focuses on detailing the complex biology of immune cells called T cells and pioneering therapies that use genetically reprogrammed T cells to specifically recognize and destroy diseased cells. These therapeutic T cells zero in on specific protein targets known as antigens, using either natural molecules called T cell receptors or synthetic molecules called chimeric antigen receptors. Chimeric antigen receptors, also known as CARs, combine elements from T cell receptors and from other immune cell-produced antibody molecules. His team’s breakthroughs are helping researchers make progress for patients who need better therapies.

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. This led to the first human trial of chimeric antigen receptor (CAR) modified T cells of defined subset composition to target CD19 on B cell malignancies, which formed the foundation for Liso-Cel, which is not FDA approved for treatment of diffuse large B cell lymphoma. 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 

• 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 or engineering therapeutic T cells
• Identifying tumor antigens that can be recognized by T cells and developing engineered TCRs or CARs using emerging principles of synthetic biology and cell signaling
• Developing new classes of synthetic receptors that instruct T cells in specific tumor eradication
• Elucidating intrinsic T cell properties that are important for effective adoptive T cell therapy, including qualities of particular T cell subsets