Adenovirus MART-1 - engineered autologous dendritic cell vaccine for metastatic melanoma

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 10(7) 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)-gamma 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-gamma 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-gamma 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 El-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdV-MART-1)/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.