Background  

An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) 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 10⁶ pfu vaccine was given by intratumoral injection, followed by 10⁸ 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 melanoma-associated 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.