Herpes simplex virus oncolytic vaccine therapy in melanoma.
BACKGROUND
Advanced melanoma is a devastating disease with a five year survival for Stage IV disease of 10 - 20% and a median survival of 6 - 18 months depending on sub-stage. Current FDA approved therapies demonstrate limited response rates, few complete remissions and no proven survival benefit. New therapies are clearly needed. JSI/34.5-/47-/GM-CSF is a herpes simplex virus-1 (OncoVEX(GM-CSF)) oncolytic vaccine therapy designed to induce local and systemic anti-tumor immune responses.


METHODS
Evolution of current herpes simplex virus oncolytic vaccines from preclinical to clinical studies from 1994 to 2010.


RESULTS
Preclinical studies have shown that herpes simplex virus-1 oncolytic vaccines generate local tumor destruction through the lytic action of the virus and local and systemic immune responses. Phase I studies demonstrated limited toxicities with no neurotoxicty. Phase II studies demonstrated durable regressions in patients with metastatic melanoma. A Phase III trial in melanoma is ongoing to determine clinical effectiveness, and a Phase III trial in head and neck cancer will initiate during 2010.


CONCLUSIONS
JSI/34.5-/47-/GM-CSF is a new generation herpes simplex virus-1 oncolytic vaccine that demonstrates direct tumor lysis and systemic immune responses. Early clinical studies have yielded preliminary evidence of activity.
Sivendran
Shanthi
S
The Mount Sinai School of Medicine, The Tisch Cancer Institute, Division of Hematology/Oncology, Department of Medicine, New York, NY 10029, USA.
Pan
Michael
M
Kaufman
Howard L
HL
Saenger
Yvonne
Y
D000818:Animals; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D019317:Evidence-Based Medicine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*; D018570:Risk Assessment; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor