Inhibition of murine melanoma growth by granulocyte-macrophage colony stimulating factor gene transfection is not haplotype specific.
Granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to inhibit the growth and progression of murine melanoma cells in syngeneic C57BL/6 (H-2b) recipient animals. We now demonstrate that this effect is not specific to melanomas derived from a single strain of mice by examining the subcutaneous growth of K1735 murine melanoma cells (H-2k) transfected with GM-CSF in a syngeneic mouse model. Non-GM-CSF-secreting melanoma cells (parental K1735 and K1735 cells transfected with the GM-CSF gene in antisense orientation) generated tumours that reached a mean volume of 4000 mm3 30-40 days, with a mean survival of 40 days after tumour cell injection. In contrast, 90% of the mice injected with three different clones of GM-CSF-producing K1735 melanomas developed no measurable tumours and were healthy and tumour-free when followed for over 300 days post-inoculation. Additionally, mice injected with GM-CSF-secreting K1735 cells developed long-lasting immunity to the parental melanoma cell line challenge in vivo. A dense neutrophilic and lymphocytic inflammatory infiltrate as well as large numbers of dendritic cells were detected only at the inoculation sites of the GM-CSF-producing melanoma cells. Thus, these studies demonstrate for the first time that GM-CSF inhibits melanoma growth in a second genetically distinct MHC tumour-host model system and further support the use of GM-CSF in clinical trials in the treatment of advanced malignant melanoma in humans.
Servicio de Dermatologia, Instituto Valenciano de Oncologia, Spain.
R
R
Botella
M D
MD
Sarradet
L E
LE
Potter
M
M
Lawley
T H
TH
Galloway
J C
JC
Ansel
C A
CA
Armstrong
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D019496:Cancer Vaccines; D002455:Cell Division; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D006239:Haplotypes / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor