Sylvester Builds Immunotherapy Momentum with Dr. Mario Sznol
A pioneer of modern cancer immunotherapy, Dr. Mario Sznol joins Sylvester Comprehensive Cancer Center to expand clinical trials and accelerate the translation of discovery into patient care.
Mario Sznol, M.D., a clinical investigator and recognized leader in cancer immunotherapy, cancer drug development and the treatment of patients with melanoma and renal cell carcinoma, has joined Sylvester Comprehensive Cancer Center, part of UHealth — the University of Miami Health System and the University of Miami Miller School of Medicine. He will support coordination of immuno-oncology research efforts, helping to bring in clinical trials and providing a clinical perspective to laboratory researchers.
“Dr. Mario Sznol is one of the physicians who helped define modern cancer immunotherapy,” said José Lutzky, M.D., chief of cutaneous oncology at Sylvester and a Miller School professor of medical oncology. “From the earliest immunotherapy trials at the National Cancer Institute to landmark checkpoint inhibitor studies at Yale, his work has shaped how cancer patients around the world are treated today. His decision to join Sylvester strengthens our national standing in immuno-oncology and accelerates our ability to translate discovery into practice through high-impact clinical trials.”
Dr. Sznol has a distinguished career in cancer immunotherapy and clinical research, and most recently served as the leader of the clinical research team for the skin and kidney program and co-leader of the cancer immunology program at Yale Cancer Center. In his earlier tenure at the National Cancer Institute (NCI), he was deeply involved in the early development of immunotherapy trials, which laid the groundwork for many of today’s most effective treatments, including checkpoint inhibitors and combination therapies. He discussed his work in the following interview, which has been edited for length and clarity.
What inspired you to focus your career on immunotherapy and oncology?
My interest in oncology began with a brief summer job in the cell biology labs at Baylor College of Medicine in Houston during high school, and oncology rotations in medical school, also at BCM. My specific interest in immunotherapy started during my fellowship at Mount Sinai in New York City, where I was first introduced to cytokine therapies (interleukin-2).
After the fellowship, I joined the NCI’s Cancer Therapy Evaluation Program (CTEP) to focus on the development of immunotherapy drugs. I was drawn to both the science underlying these therapies and the potential for immunotherapy to produce dramatic, long-term responses in a subset of patients with advanced disease.
Looking back, what are the most significant milestones from your time at Yale and the National Cancer Institute?
At NCI, and specifically within CTEP, I was involved in the clinical development of a very large number of immune modulators for cancer, at a time when the field was rapidly evolving and beginning to understand how the immune system actually worked and how it interacted with cancer.
At Yale, my colleagues and I focused on trials of immune checkpoint inhibitors, particularly anti-PD-1 and the combination of anti-PD-1 and anti-CTLA-4. We were key participants in those initial trials and helped to identify the initial signals of clinical activity and approaches to manage toxicity.
How has your work with immune checkpoint inhibitors and cytokine therapies shaped cancer treatment today?
I was part of a team of very dedicated individuals who demonstrated the potential of immune therapy to produce meaningful benefit for patients and, in a small subset, long-term remissions and possibly a cure for life-threatening disease with no other treatment options. Today, anti-PD-1 is possibly the most active agent for cancer treatment and is used in almost all malignancies. Moreover, the clinical activity of anti-PD-1 led to substantial investment in developing other types of immune therapies for cancer.
What excites you most about the next generation of immunotherapies and their potential impact on patient care?
It has been much more difficult to identify new, effective immunotherapies for patients who do not respond to, or become resistant to, anti-PD-1 or combinations that include anti-PD-1. There are multiple potential mechanisms of non-response.
In the near term, the most promising approaches will involve cell therapies and bispecific T-cell engagers, and perhaps a subset of engineered cytokines that can be used to support the latter therapies. There are new generations of agents that modulate the function of intratumoral myeloid cells, which either lead to direct tumor killing or enable adaptive T cell responses.
Although cancer vaccination in various forms is generating a great deal of interest and there are preliminary, promising data, I believe there are substantial, but surmountable, challenges. I plan to focus my clinical efforts on agents that enhance tumor T cell infiltration, expansion and interactions at the tumor/T cell interface. Still, there are many other important and legitimate areas of research.
What attracted you to Sylvester and what opportunities do you see here?
I’ve had a connection to Miami for many years and, at this stage of my life, I wanted to live here and also wanted to contribute to the community. I was drawn to UM because of the substantial growth and evolution of Sylvester, led by Dr. Stephen Nimer, and the work that Dr. Jose Lutzky has done in building and growing both the cutaneous oncology program and the overall clinical research apparatus. I found a substantial commitment to both clinical and lab-based research. So, there will be many opportunities to bring novel clinical trials to the institution and to assist in transitioning institutional science to the clinic.
How do you plan to advance Sylvester’s immunotherapy research and clinical programs?
I’m a clinician, not a lab-based scientist, so I will need to collaborate with colleagues at UM to expand research opportunities. The first step in building any coordinated program is to identify and develop relationships with institutional scientists focused on cancer immunology or immunology applicable to cancer. I hope to leverage my prior experience and relationships to expand clinical research, particularly in immune therapy.
What do you believe patients should understand about immunotherapy as part of their treatment journey?
Immunotherapy is not the right choice for every patient and, despite our best efforts, it only works in a subset. It can also be associated with toxicities but, fortunately, these can be managed and reversed easily in the vast majority. Nevertheless, it is one of the few cancer treatment modalities that can produce long-term remissions of advanced disease and can extend life in combination with other more traditional cancer treatments in many patients. Every cancer patient should ask if immunotherapy in some form is an appropriate treatment for their disease.
If you could predict one breakthrough in cancer treatment over the next decade, what would it be?
It’s hard to pick just one. The data suggest the T-cell engagers will have increasing impact across diseases. Although perhaps not curative, they will provide substantial benefit, and the field is only beginning to address combinations to increase their effectiveness. Much of this comes from advances in defining tumor targets and protein engineering.
Outside of immune therapy, increasing the specificity of drug delivery should improve risk/benefit, for example, the antibody drug conjugates. Advances in cancer biology and drug design may lead to new targets and new drugs for targets previously considered undruggable, such as proximity-based target degradation. And I suspect we may have in vivo, cancer-specific gene editing in the not-too-distant future.
What advice would you give to young physicians entering oncology?
If it’s for pure clinical investigators, I advise them to focus on diseases for which we don’t have good options at this time. It allows them to make a major impact on future patients.
What do you like to do in your free time?
Play as much tennis as my body will tolerate.
Tags: cancer research, clinical trials, Dr. Mario Sznol, immunology, immunotherapy, Newsroom, Sylverster Comprehensive Cancer Center