Log in |
Howard L. Kaufman MD, Dae Won Kim MD, Gail DeRaffele RN, Josephine Mitcham BS, Rob S. Coffin PhD, Seunghee Kim-Schulze PhD
View full article HTML | View full article PDF | Download Citation
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.
Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an oncolytic herpesvirus encoding GM-CSF (OncovexGM-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).
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.
Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of OncovexGM-CSF induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.
Go to Issue Contents
Add this article to your Personal Archive
Effective January 2013, there will be a processing fee of $50 USD for each initial new submission of an Annals article, excluding editorials. Submitted new manuscripts will not enter the review process until the submission fee has been paid. . There will be no processing fee associated with resubmitted manuscripts.
HIGHLIGHTED VIDEO OF THE MONTH
Lymphatic Mapping and Sentinel Node Biopsy in the Colonic Mesentery by Natural Orifice Transluminal Endoscopic Surgery (NOTES) by R. A. Cahill MD, FRCS, S. Perretta MD, J. Leroy MD, B. Dallemagne MD, and J. Marescaux MD, FRCS, FACS. Annals of Surgical Oncology. Volume 15, Number 10, DOI: 10.1245/s10434-008-9952-8
Annals of Surgical Oncology is copyrighted by the Society of Surgical Oncology
© Springer Healthcare Ltd. A part of Springer Science+Business Media