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.
The Mount Sinai School of Medicine, The Tisch Cancer Institute, Division of Hematology/Oncology, Department of Medicine, New York, NY 10029, USA.
Shanthi
S
Sivendran
Michael
M
Pan
Howard L
HL
Kaufman
Yvonne
Y
Saenger
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