Our lab team is focused on advancing the field of adoptive cellular immunotherapy, and rapidly translating new treatments for patients with otherwise limited options. Having trained at Memorial Sloan Kettering at a time when the first CD19 targeted CAR T cell therapy trial for adults with relapsed/refractory B cell ALL was ongoing, Dr. Smith was inspired to develop novel CAR T cell vectors that would extend this therapeutic modality to patients with the CD19-negative malignancy, Multiple Myeloma. Trials investigating vectors stemming from this work and the work of many others demonstrate that CAR T cell therapy can induce frequent and deep remissions for patients with relapsed/refractory hematologic malignancies, however, relapse is still far to common. Further, solid tumors are still generally refractory to the current generation of CAR T cell therapies, posing unique challenges to overcome.

Mechanisms of relapse/resistance can be broadly defined to include: (1) Tumor mediated mechanisms, such as antigen escape; (2) CAR T cell mediated mechanisms, such as lack of maximal persistence caused by sub-optimal signaling through the CAR, or anti-CAR immunity; and (3) Host mediated mechanisms, such as tumor microenvironment immune suppression.

In an effort to overcome the limitations of current adoptive cellular therapies, the Eric Smith Lab studies murine models and patient samples to better understand the biology of T cells, tumor cells, and the microenvironment underlying these resistance mechanisms. Jumping off from these results and the works of others, our main focus is to design and evaluate novel genetically modified immune effector cell therapy approaches. Capitalizing on our prior experience, we rapidly translate the most promising for clinical investigation.