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Purpose-Prior studies show that intramuscular (IM) injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) induces CD8+ T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a pilot clinical trial comparing IM injection with particle-mediated epidermal delivery (PMED).Experimental Design-Human leukocyte antigen (HLA)-A*0201+ disease-free melanoma patients were randomized to the PMED or IM arm, receiving 8 vaccinations over 4 months. Patients received 4 μg or 2000 μg per injection, respectively, of mouse gp100 DNA. Peripheral blood mononuclear cells (PBMCs) were collected, cultured with gp100 peptides and analyzed by tetramer and intracellular cytokine staining (ICS) for responses to HLA-A*0201-restricted gp100 epitopes [gp100 [209][210][211][212][213][214][215][216][217] (ITDQVPFSV) and gp100 280-288 (YLEPGPVTA)].Results-Twenty seven patients with stage IIB-IV melanoma were analyzable for immune response. The only common toxicity was grade I injection site reaction in 9 patients with no intergroup difference, while one dose-limiting toxicity of acute hypersensitivity occurred in a PMED patient with undiagnosed gold allergy. Four of 27 patients produced gp100 tetramer+CD8+ T cells, all carrying the CCR7 lo CD45RA lo effector-memory phenotype. Five of 27 patients generated interferon-γ+ (IFN-γ) CD8+ T cells, one who was also tetramer-positive. Overall, vaccination induced a response in 30% of patients, which was not significantly associated with study arm or clinical outcome. However, the PMED group showed a trend toward increased IFN-γ +CD8+ T cell generation (p=0.07).Conclusion-A comparable efficacy and safety profile was demonstrated between the IM and PMED arms, despite a significantly decreased dose of DNA used for PMED injection.

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