It is a promising time for cellular therapy, and combinations with gene modification or other systemic or local therapies bode well for solid tumor development of this TIL therapy platform.
Robert L. Ferris, MD, PhD
Director
Hillman Cancer Center
University of Pittsburgh
Medical Center
Pittsburgh, PA
Despite the rapid application and development of cellular therapies for hematologic malignancies, including chimeric antigen receptor cells, the field of cellular therapy for solid tumors has primarily been tumor infiltrating lymphocyte products. As with most cancer immunotherapies developed in recent decades, metastatic melanoma has been the proving ground for new agents. At the European Society for Medical Oncology Immuno-Oncology Congress in December, the lifileucel TIL therapy data (C-144-01 study, NCT02360579) were presented, now with years of follow-up. These findings led to the FDA approval for the treatment of patients with advanced melanoma who have progressed following anti-PD1/PD-L1 and/or targeted therapy.
Besides response rates, durability is the hallmark of successful cancer immunotherapy. With an overall response rate of over 31%, including several complete responders, it should be acknowledged that this is a very impressive dataset with durability. Clearly, there were more responders among patients with fewer liver and brain lesions, less tumor burden in terms of median target lesions and size, and fewer baseline lesions. Indeed, most toxicities came from the nonmyeloablative conditioning regimen.
In addition, a response rate of over 30% with a sizable number of deep and even complete responses in the 48 patients is reassuring and may translate to other tumor types with initial shorter-term follow-up data. Further work may incorporate systemic therapies to combine with the cellular product to maintain activity and avoid metabolic dysfunction and exhaustion.
It is a promising time for cellular therapy, and combinations with gene modification or other systemic or local therapies bode well for solid tumor development of this TIL therapy platform.
Selective local therapy such as stereotactic radiation and intralesional or systemic oncolytic viruses may help to optimize this promising type of treatment. Of course, the logistical issues persist, including harvesting tumor that often requires a surgical procedure, leading to a 3- to 4-week good manufacturing practice (GPM) cell therapy production, and need to be overcome. Now, an increasing number of institutions have this GMP cell therapy production capacity with traditional clean rooms, as well as more portable GMP-grade bioreactor incubators for democratization of this type of therapy, which some patients cannot tolerate. There has also been a reduction in shipping and production times. It is a promising time for cellular therapy, and combinations with gene modification or other systemic or local therapies bode well for solid tumor development of this TIL therapy platform.
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