Interferon alfa-2b treatment following therapeutic vaccination with mRNA electroporated dendritic cells results in skin depigmentation and tumor regression in patients with advanced melanoma

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8537 Background: Therapeutic vaccination with autologous dendritic cells (DC) and Interferon alfa-2b (IFNa) both have low activity in patients with advanced melanoma. Combination therapy might be advantageous because of their complementary mechanism of action. Methods: We are investigating the safety and activity of an autologous DC-based melanoma vaccine in patients with advanced melanoma in a single institution phase IB clinical trial. Following leucapheresis and enrichment in a semi-closed culture system, adherent PBMC are cultured in IL-4 and GM-CSF supplemented medium for 6 days and cryo-preserved. Upon thawing, 15.106 DC are electroporated with synthetic mRNA that encodes a fusion protein between LAMP and one of 6 melanoma associated antigens (MAGE.A-1, MAGE.A-3, MAGE.C2, MELANA/MART1, Tyrosinase and gp100). DC vaccines are administered by 6 bi-weekly ID/SC injections and every 6–8w thereafter. Results: 15 pts (10M/5F; median age 52, range 27–72) with stage IIIC-IV melanoma have been recruited. Ten pts were able to receive ≥ 6 vaccinations. Toxicity was limited to grade 1 or 2 local skin reactions at the vaccine administration sites in all pts. Two pts had a regression of subcutaneous (sc) metastases during DC vaccination and one of these pts remains disease-free after 18 mths of follow-up (following the resection of a single residual metastasis). An additional pt remains disease-free following surgery of in transit metastases at 8 months of follow-up. Three out of four pts who were treated with IFNa-2b (5 106 U 3x/week sc) at progression developed skin depigmentation (leucoderma punctata) and in 2 of these pts an objective tumor response was documented (PR and CR, including complete regression of skin, lymph, liver and skeletal metastases). Both responses are ongoing at 9 and 11 months of follow-up. Conclusions: These preliminary observations indicate a potential for IFNa-2b to mediate auto-immune breakthrough and tumor regression in advanced melanoma patients vacinated with a mRNA electroporated DC-vaccine. Further investigation of this combination immunotherapy in advanced melanoma patients is ongoing. No significant financial relationships to disclose.