Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice.
Replication-competent, attenuated mutants of herpes simplex virus type 1 (HSV-1) have been shown to be efficacious for tumor therapy. However, these studies did not address the consequences of prior exposure to HSV, as will be the case with many patients likely to receive this therapy. Two strains of mice, A/J and BALB/c, were infected with wild-type HSV-1 by intraperitoneal injection and the immune response was determined by plaque reduction assay for neutralizing antibody and ELISA for IgG and IgM. Syngeneic tumors, N18 neuroblastoma and CT26 colon carcinoma, were implanted subcutaneously in HSV-1 seropositive and naive A/J and BALB/c mice, respectively. Established tumors were subsequently treated intratumorally with a multi-mutated HSV-1, G207. G207 inhibited tumor growth to a similar extent whether the mice were seropositive or not. We next examined the effect of multiple intratumoral inoculations of a 10-fold lower dose of G207 on tumor growth. In the multiple treatment group (biweekly for 3 weeks), 75% of tumors were cured, whereas no cures were seen in the single treatment group. We conclude that HSV seropositivity should not deleteriously affect the efficacy of G207 tumor therapy, and multiple inoculations of virus should be considered for clinical evaluation.
Chahlavi
A
A
Molecular Neurosurgery Laboratory, Department of Neurosurgery, Georgetown University Medical School, Washington DC 20007, USA.
Rabkin
S
S
Todo
T
T
Sundaresan
P
P
Martuza
R
R
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011897:Random Allocation; D014407:Tumor Cells, Cultured
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M