Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction.
Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.
Abe
J
J
Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Tokyo, Japan.
Wakimoto
H
H
Yoshida
Y
Y
Aoyagi
M
M
Hirakawa
K
K
Hamada
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014612:Vaccines / Q000276:immunology
D011994:Recombinant Proteins; D014612:Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor