Suppression of melanoma growth and metastasis by DNA vaccination using an ultrasound-responsive and mannose-modified gene carrier.
DNA vaccination has attracted much attention as a promising therapy for the prevention of metastasis and relapse of malignant tumors, especially highly metastatic tumors such as melanoma. However, it is difficult to achieve a potent cancer vaccine effect by DNA vaccination, since the number of dendritic cells, which are the major targeted cells of DNA vaccination, is very few. Here, we developed a DNA vaccination for metastatic and relapsed melanoma by ultrasound (US)-responsive and antigen presenting cell (APC)-selective gene carriers reported previously, named Man-PEG₂₀₀₀ bubble lipoplexes. Following immunization using US exposure and Man-PEG(2000) bubble lipoplexes constructed with pUb-M, which expresses ubiquitylated melanoma-specific antigens (gp100 and TRP-2), the secretion of Th1 cytokines (IFN-γ and TNF-α) and the activities of cytotoxic T lymphocytes (CTLs) were specifically enhanced in the presence of B16BL6 melanoma antigens. Moreover, we succeeded in obtaining potent and sustained DNA vaccine effects against solid and metastatic tumor derived from B16BL6 melanoma specifically. The findings obtained from this study suggest that the gene transfection method using Man-PEG₂₀₀₀ bubble lipoplexes and US exposure could be suitable for DNA vaccination aimed at the prevention of metastatic and relapsed cancer.
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Keita
K
Un
Shigeru
S
Kawakami
Ryo
R
Suzuki
Kazuo
K
Maruyama
Fumiyoshi
F
Yamashita
Mitsuru
M
Hashida
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008358:Mannose / Q000737:chemistry*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D058950:Melanoma-Specific Antigens / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D054875:Ubiquitination; D014465:Ultrasonics; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; D016207:Cytokines; D008081:Liposomes; D058950:Melanoma-Specific Antigens; D012333:RNA, Messenger; D019444:Vaccines, DNA; D011092:Polyethylene Glycols; D008358:Mannose