Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors.
Gene therapy-induced expression of immunostimulatory molecules at tumor cell level may evoke antitumor immune mechanisms by recruiting and enhancing viability of antigen-processing cells and specific tumoricidal lymphocytes. The antitumor efficacy of a plasmid, coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) and the B7-1 costimulatory immune molecule, delivered into growing solid tumors by electroporation was investigated. Murine fibrosarcomas (JBS) growing in Balb/C mice (<or=100 mm3) were transfected with GM-CSF/B7-1-expressing plasmid. Complete tumor regression occurred in greater than 60% of treated animals. This response was systemic, durable and tumor specific, with all responding animals resistant to repeat tumor challenge. Using a liver metastatic model, effective cure of distal metastases was achieved following treatment of the primary subcutaneous tumor. This treatment strategy could be applicable in the clinical setting for effective elimination of both primary tumors and associated metastatic disease.
Collins
C G
CG
Cork Cancer Research Centre, Mercy University Hospital and Leslie C Quick Jnr Laboratory, University College Cork, Cork, Ireland.
Tangney
M
M
Larkin
J O
JO
Casey
G
G
Whelan
M C
MC
Cashman
J
J
Murphy
J
J
Soden
D
D
Vejda
S
S
McKenna
S
S
Kiely
B
B
Collins
J K
JK
Barrett
J
J
Aarons
S
S
O'Sullivan
G C
GC
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor / Q000473:pathology; D017690:Cell Transplantation; D003601:Cytotoxicity Tests, Immunologic; D018274:Electroporation / Q000295:instrumentation / Q000379:methods; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D010957:Plasmids / Q000235:genetics; D014162:Transfection
D018122:B7-1 Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor