Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma

Ann Surg Oncol. 2010 Mar;17(3):718-30. doi: 10.1245/s10434-009-0809-6.


Background: An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte-macrophage colony-stimulating factor (GMCSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.

Methods: Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an oncolytic herpesvirus encoding GM-CSF (Oncovex(GM-CSF)). An initial priming dose of 10(6) pfu vaccine was given by intratumoral injection, followed by 10(8) pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4(+)FoxP3(+) regulatory T cells (Treg), CD8(+)FoxP3(+) suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC).

Results: Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanomaassociated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions.

Conclusions: Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of Oncovex(GM-CSF) induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Antigens, Neoplasm
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Genetic Therapy*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Injections, Intralesional
  • MART-1 Antigen
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Proteins
  • Neoplasm Staging
  • Oncolytic Viruses / genetics*
  • Simplexvirus / genetics*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Transduction, Genetic
  • Vaccination


  • Antigens, Neoplasm
  • Cancer Vaccines
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor