Intratumoral IL-12 Injections Shrink Melanoma and Merkel Cell Tumors
Intratumoral injections of plasmid DNA encoding interleukin-12 (IL-12), facilitated in its delivery by electroporation, results in tumor regression in patients with both metastatic melanoma and Merkel cell carcinoma, according to findings reported at the 2013 World Cutaneous Malignancies Congress on Sunday, July 27, in San Diego.
“IL-12 is a very powerful immune-stimulating protein. There was excitement for IL-12 in the 1980s and 1990s, but systemic toxicity prevented further development of it. Since that time, investigators have been trying to deliver IL-12 in creative ways, and this is one example of such an approach,” said Shailender Bhatia, MD, of the Seattle Cancer Care Alliance in Seattle.
Electroporation can transduce, with high efficiency, plasmid DNA directly into melanoma and Merkel cell carcinoma cells. The IL-2 expression remains concentrated within the tumor microenvironment, with no systemic spillage. This stimulates innate and adaptive immune responses while avoiding toxicities associated with systemic IL-12 therapy, he explained to The ASCO Post.
Lesion Regression Observed in Melanoma
In a phase II multicenter study in 13 patients with metastatic melanoma reported as a poster at this meeting, patients were injected intratumorally with IL-12 (0.5 mg/mL) followed immediately by electroporation. Treatment was delivered to up to four lesions on days 1, 5, and 8 every 6 weeks, for a total of 37 treated lesions.
The study was led by Adil Daud, MD, of the University of San Francisco, and Dr. Bhatia was a coinvestigator.
At the day 90 assessment, 82% of target lesions demonstrated a response after only a single cycle of treatment, with 47% being complete responses. Target lesions demonstrated a 68% durable response rate (≥ 6 months) at 90 days.
Two patients have been assessed 180 days after the first cycle of treatment. One had a complete response and continues to remain disease-free past 1 year. The second had stable disease at day 180 but subsequently showed disease progression. The data are not yet analyzed for the remaining patients.
Blood samples taken at baseline and day 90 suggested that plasmid delivery of IL-12 can result in a decrease in “exhausted T cells,” the researchers reported.
Merkel Cell Carcinoma Responds Well
Because of the encouraging results seen for this approach in melanoma, a phase II study was begun in Merkel cell carcinoma, and results were similar, said Dr. Bhatia, who lectured on emerging therapies for Merkel cell carcinoma at the meeting.
He said complete responses were observed within weeks of injections, and noninjected lesions elsewhere on the body also regressed within weeks or months. Increased intratumoral CD8-positive infiltration was observed in 50% of patients.
“This suggests that we are getting a successful immune response,” Dr. Bhatia said. “The big advantage of this approach is its localized delivery without the production of systemic side effects.”
“The hope is we could combine this local therapy with a systemic therapy,” he added, perhaps a novel immunotherapeutic agent such as ipilimumab (Gleevec) or anti-PD-1. “It would be like starting a fire with local treatment, and using drugs to spread the fire throughout the forest.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
