In vivo bioluminescence visualization of antitumor effects by human MUC1 vaccination.
Recently, the use of a cancer deoxyribonucleic acid (DNA) vaccine encoding tumor-associated antigens has emerged as an immunotherapeutic strategy. In this study, we monitored tumor growth inhibition by pcDNA3-hMUC1 immunization in mice using optical imaging. To determine the anti-hMUC1-associated immune response generated by pcDNA3.1 or pcDNA3-hMUC1, we determined the concentration of interferon-gamma (IFN-gamma) protein and CD8+IFN-gamma cell numbers among lymphocytes from the draining lymph nodes of mice immunized with pcDNA3.1 or pcDNA3-hMUC1. After subcutaneously injecting CT26/hMUC1-Fluc into mice immunized with pcDNA3-hMUC1, we monitored in vivo tumor growth inhibition using an optical imaging method. The concentration of IFN-gamma protein in pcDNA3-hMUC1 was higher than that of the pcDNA3.1 group (2.7 < or = 0.08 ng/mL and 1.6 +/- 0.07 ng/mL, respectively, p < .001. The number of hMUC1-associated CD8+IFN-gamma cells in pcDNA3-hMUC1-immunized animals was 30-fold higher than in the pcDNA3.1 group. Bioluminescent images showed tumor growth inhibition in pcDNA3-hMUC1 immunized animals up to 25 days after immunization. A good correlation (r2 = .9076: pcDNA3/hMUC1 group; r2 = .7428: pcDNA3.1 group) was observed between bioluminescence signals and tumor weights in two mice in each group. We conclude that optical bioluminescent imaging offers a useful means of monitoring the antitumor effects of cancer DNA immunization in living animals.
Jeon
Yong Hyun
YH
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Choi
Yun
Y
Kim
Hyun Joo
HJ
Kang
Joo Hyun
JH
Kim
Chul Woo
CW
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Chung
June-Key
JK
D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D016207:Cytokines; C060192:MUC1 protein, human; D018396:Mucin-1; D019444:Vaccines, DNA; D007371:Interferon-gamma; D049409:Luciferases, Firefly