Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma

J Clin Invest. 2005 Jul;115(7):1903-12. doi: 10.1172/JCI24624. Epub 2005 Jun 2.


Immunotherapy for the treatment of metastatic melanoma remains a major clinical challenge. The melanoma microenvironment may lead to local T cell tolerance in part through downregulation of costimulatory molecules, such as B7.1 (CD80). We report the results from the first clinical trial, to our knowledge, using a recombinant vaccinia virus expressing B7.1 (rV-B7.1) for monthly intralesional vaccination of accessible melanoma lesions. A standard 2-dose-escalation phase I clinical trial was conducted with 12 patients. The approach was well tolerated with only low-grade fever, myalgias, and fatigue reported and 2 patients experiencing vitiligo. An objective partial response was observed in 1 patient and disease stabilization in 2 patients, 1 of whom is alive without disease 59 months following vaccination. All patients demonstrated an increase in postvaccination antibody and T cell responses against vaccinia virus. Systemic immunity was tested in HLA-A*0201 patients who demonstrated an increased frequency of gp100 and T cells specific to melanoma antigen recognized by T cells 1 (MART-1), also known as Melan-A, by ELISPOT assay following local rV-B7.1 vaccination. Local immunity was evaluated by quantitative real-time RT-PCR, which suggested that tumor regression was associated with increased expression of CD8 and IFN-gamma. The local delivery of vaccinia virus expressing B7.1 was well tolerated and represents an innovative strategy for altering the local tumor microenvironment in patients with melanoma.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / therapeutic use
  • CD8 Antigens / genetics
  • Female
  • Gene Expression
  • Genetic Therapy*
  • HLA-A Antigens
  • HLA-A2 Antigen
  • Humans
  • Immunotherapy*
  • Injections, Intralesional
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • MART-1 Antigen
  • Male
  • Melanoma / genetics
  • Melanoma / immunology
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Proteins / immunology
  • T-Lymphocytes / immunology
  • Vaccinia virus / genetics*
  • Vaccinia virus / immunology*


  • Antigens, Neoplasm
  • B7-1 Antigen
  • CD8 Antigens
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Interleukin-10
  • Interferon-gamma