2016 Clinical Research Forum Top 10 | Resiquimod Therapy of Cutaneous T-Cell Lymphoma
The principal investigator brought together a large research team with unique research skills to study the effects of potently activating the innate immune response with the Toll-like receptor (TLR) agonist Resiquimod on the progress of tumor lesions among patients with cutaneous T-cell lymphoma (CTCL). Presently, the only known cure for CTCL, which is a lymphoma of skin trafficking T-cells, is allogeneic stem cell transplantation. However, our laboratory based research had suggested that Resiquimod, which is a TLR 7/8 agonist, could broadly activate the immune response of patients with advanced forms of CTCL. With provision of the drug from Spirig Pharma in Switzerland, and funding from the National Cancer Institute and the Division of Orphan Products, FDA, a phase I trial was conducted. Resiquimod was applied as a gel to a maximum of only 4 skin plaques and tumors. Eleven of 12 patients significantly improved, including two patients with highly refractory and active disease for more than 10 years, each of whom experienced complete remission which has been sustained more than two years beyond treatment discontinuation. We were able to demonstrate that malignant T-cells could be eradicated from treated lesions. Uniquely, even untreated distant lesions regressed indicating that Resiquimod could be well absorbed through the skin and could activate the systemic antitumor immune response. We did confirm that circulating dendritic cells and NK cells were activated.
Thus, Resiquimod produced exceptionally high response rates, induced regression of even untreated lesions, eradicated malignant cells from treated lesions and activated circulating immune cells. The implications of these observations are significant for other skin malignancies including malignant melanoma, squamous cell carcinoma and Merkel cell carcinoma.
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