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

J Immunother. 2008 Apr;31(3):294-309. doi: 10.1097/CJI.0b013e31816a8910.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • 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
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunotherapy, Active* / adverse effects
  • MART-1 Antigen
  • Male
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / immunology*
  • Neoplasm Staging
  • Protein Engineering
  • Transduction, Genetic
  • Treatment Outcome


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Immunodominant Epitopes
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins