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J Immunother ; 31(3): 294-309, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18317358

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 CD+8 and CD4+ T cells. Metastatic melanoma patients received 3 injections of 10(6) 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 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.


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines , Dendritic Cells/immunology , Immunotherapy, Active , Melanoma/therapy , Neoplasm Proteins/immunology , Adenoviridae/genetics , Adenoviridae/immunology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/chemistry , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Female , Humans , Immunodominant Epitopes/immunology , Immunotherapy, Active/adverse effects , MART-1 Antigen , Male , Melanoma/immunology , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Neoplasm Proteins/chemistry , Neoplasm Staging , Protein Engineering , Transduction, Genetic , Treatment Outcome
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