Oncolytic therapy using a mutant type-1 herpes simplex virus and the role of the immune system.
BACKGROUND
Herpes simplex virus (HSV)-1716, a replication-restricted herpes simplex virus type 1, has shown efficacy as an oncolytic treatment for central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma. We evaluated the efficacy of HSV-1716 in a murine lung cancer model, Lewis lung carcinoma.


METHODS
Lewis lung carcinoma cells were infected with HSV-1716 and implanted in the flanks of mice at varying ratios of infected to uninfected cells. Tumor burden was assessed by measurement of the weight of the tumor nodule. The role of the immune system was examined by performing experiments in both immunocompetent and SCID mice. Tumors were implanted in the opposite flank to evaluate the vaccine effect.


RESULTS
In immunocompetent and SCID animals, ratio of 1:10 (infected-to-uninfected) cells completely prevented tumor formation and ratio of 1:100 suppressed tumor growth. Established tumors at a distant site in the groups receiving HSV-1716 infected cells showed no difference in size versus control, suggesting absence of a vaccine effect.


CONCLUSIONS
We conclude that HSV-1716 may provide a oncolytic therapy for lung cancer even in the absence of immune system induction and a "carrier" cell could potentially deliver this vector.
Lambright
E S
ES
Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, USA.
Caparrelli
D J
DJ
Abbas
A E
AE
Toyoizumi
T
T
Coukos
G
G
Molnar-Kimber
K L
KL
Kaiser
L R
LR
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015275:Tumor Lysis Syndrome / Q000276:immunology* / Q000821:virology; D014780:Viruses / Q000235:genetics / Q000276:immunology*