In the 1990s, Dr. Riddell and colleagues performed the first studies of T cell therapy to block life-threatening reactivation of cytomegalovirus after allogeneic hematopoietic stem cell transplantation (HCT). This work provided proof-of-principle that antigen-specific T cells can be used in humans to boost T cell immunity to a virus, and paved the way for studies using T cell therapy to treat cancer. Riddell’s lab developed improved techniques for isolation, expansion, genetic modification and reinfusion of T cells, and for monitoring safety, persistence, migration and function after transfer. Many of these methods are now widely used in the field.
Subsequent work has focused on developing techniques to express specific genes that redirect T cell specificity to cancer cells and/or improve their function, on identifying the most effective types of T cells to use for cancer immunotherapy, and on evaluating the safety and efficacy of novel T cell therapies in early phase clinical trials in many types of cancer.
Dr. Riddell’s lab continues to focus on establishing the principles for the safe and effective use of T cell immunotherapy to treat cancer. This effort encompasses fundamental studies of T cell differentiation and signaling, the development of preclinical animal models, clinical translation, and novel applications of synthetic biology to enhance therapeutic T cells. Demonstrations in preclinical models that naïve and specific memory T cell subsets can have superior persistence and efficacy after adoptive transfer informed new methods to rapidly isolate defined cell populations for clinical trials using T cells modified with specific chimeric antigen receptors (CARs) or T cell receptors (TCRs).