Advances in Hematologic Malignancies
Issue 14, Spring 2021
Why did you decide to work in oncology?
As a second-year medical student at Mount Sinai in East Harlem, I helped start a free internal medicine clinic for uninsured local patients. Two of the first patients I took care of presented with constitutional symptoms and were ultimately diagnosed
with blood cancers. Through these early experiences, I found that the field of oncology provided the opportunity to profoundly impact patients' lives. Further, as an MD/PhD in training, at a time when there was a rapid expanse of precision medicine,
gene therapy, advances in our understanding of immunology, and ultimately the dawn of clinically effective immunotherapy, I found the future of bench to bedside research occurring in the field compelling.
Tell us about the condition(s) you specialize in. Why is this an area of interest to you? What led you to focus here?
I specialize in cellular therapy and multiple myeloma (MM). I have always found the approach and challenges to the diagnosis and management of blood cancers rewarding.
Within blood cancers, my research led me to my clinical specialization of MM. I was fortunate to be a medical oncology fellow at Sloan Kettering during the first clinical trial anywhere of CD19-targeted CAR T-cell therapy for adults with relapsed/refractory ALL. Having cared for some of these early patients, I wanted to extend CAR T-cell therapy to CD19-negative malignancies. It made all the sense in the world to me that I should focus my efforts on bringing CAR T-cell
therapy to MM, a bone marrow-based malignancy where current therapies rarely, if ever, resulted in cure.
What are the main challenges in this area? How do you address these challenges?
Now that BCMA-targeted CAR T-cell therapies developed by our group and others are generating unprecedented response rates for the most difficult-to-treat cases of MM, the biggest challenge is relapse. For MM, as well as for ALL and large cell lymphoma,
we need to develop cellular therapies that will eradicate every last malignant cell, resulting in cure far more frequently. My lab group is tackling this challenge by developing and translating to the clinic novel cell therapy approaches. For example,
we described a novel target for immunotherapy of MM, GPRC5D, and developed CAR T cells against this antigen. A multi-center trial stemming from this work recently opened at Dana-Farber for heavily pre-treated MM patients, including those who have
relapsed after BCMA-targeted therapy. We have also published on dual-targeted cell therapy approaches and are pursuing several other potential advances in the field of adoptive cellular therapy towards this goal of more frequently obtaining highly
Describe your vision for the research work you're leading in cell therapies.
Adoptive cellular therapies are programmable living drugs. Broadly speaking, my lab aims to make these therapies more effective, safer, and more accessible. In addition to our goal of enhancing the cure rate for MM, we are aiming to make inroads effectively
extending this modality to additional blood cancers and solid tumors. We focus on applying the most recent advances in genetic engineering and cellular manufacturing to advance the field of adoptive cellular immunotherapy.
What are you most excited about in the area of cell therapies? What holds promise for patients?
The ceiling for what we can do with genetically engineered cellular therapies is so incredibly high I am perennially excited about what is coming next. As CRISPR-based tools gain more traction as clinical products, more progress is made for solid tumors,
and patients are treated earlier in the disease course, I expect that a single treatment of a cellular therapy will replace months and months of chemotherapy, simultaneously increasing the frequency of cure and dramatically decreasing the burden that
treatment makes on the quality of life of our patients.
What do you like to do when you're not doing research/caring for patients? What do you do for fun?
Having recently moved from New York, my wife, two daughters, and I are enjoying getting to know Boston and the surrounding areas. We frequently spend our weekends biking along the banks of the Charles River, hiking a trail in the nearby Blue Hills, or
exploring one of the charming towns or beaches within an hour or so drive from our newly adopted hometown.
Learn more about Dr. Smith's research.