Adenovirus MART-1–engineered Autologous Dendritic Cell Vaccine for Metastatic Melanoma

Abstract

We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1). This vaccine was designed to activate MART-1–specific CD8⁺ and CD4⁺ T cells. Metastatic melanoma patients received 3 injections of 10⁶ or 10⁷ DCs, delivered intradermally. Cell surface phenotype and cytokine production of the DCs used for the vaccines were tested, and indicated intermediate maturity. CD8⁺ T-cell responses to MART-1_27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4⁺ T-cell responses to MART-1_51-73 were followed by IFN-γ ELISPOT. We also measured antigen response breadth. Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-γ ELISPOT. Twenty-three patients were enrolled and 14 patients received all 3 scheduled DC vaccines. Significant CD8⁺ and/or CD4⁺ MART-1–specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo. Responses in CD8⁺ and CD4⁺ T cells to additional antigens were noted in 2 patients. The AdVMART1-transduced DC vaccine was safe and immunogenic in patients with metastatic melanoma.