AV.TK-mediated killing of subcutaneous tumors in situ results in effective immunization against established secondary intracranial tumor deposits.
Gene transfer vectors expressing herpes simplex thymidine kinase (HSVtk), in addition to direct killing of tumor cells, often have an associated local "bystander effect" mediated by metabolic coupling of tumor cells. A systemic antitumor effect mediated by the immune system, termed the distant bystander effect, has also been reported. We have observed the development of cytotoxic T-lymphocyte (CTL) populations and long-lasting antitumor immunity following treatment of subcutaneous tumors with an adenoviral vector expressing HSVtk (AV.TK) and ganciclovir (GCV) in rat glioma model. This vaccination effect seen with AV.TK/GCV treatment of subcutaneous tumor could even abrogate or retard growth of previously established secondary intracranial tumors.
Okada
T
T
Clinical Gene Therapy Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Shah
M
M
Higginbotham
J N
JN
Li
Q
Q
Wildner
O
O
Walbridge
S
S
Oldfield
E
E
Blaese
R M
RM
Ramsey
W J
WJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D009374:Neoplasms, Experimental / Q000628:therapy; D051381:Rats; D011916:Rats, Inbred F344; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D013937:Thymidine Kinase; D015774:Ganciclovir