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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kaufman, HL; Deraffele, G; Mitcham, J; Moroziewicz, D; Cohen, SM; Hurst-Wicker, KS; Cheung, K; Lee, DS; Divito, J; Voulo, M; Donovan, J; Dolan, K; Manson, K; Panicali, D; Wang, E; Hörig, H; Marincola, FM

Published Date

  • July 2005

Published In

Volume / Issue

  • 115 / 7

Start / End Page

  • 1903 - 1912

PubMed ID

  • 15937544

Pubmed Central ID

  • 15937544

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI24624

Language

  • eng