DNA vaccination against HuD antigen elicits antitumor activity in a small-cell lung cancer murine model.
There is a clinically significant correlation between the presence of an antibody against the paraneoplastic encephalomyelitis antigen HuD and the limitation of tumor spread in patients with small-cell lung cancer (SCLC). This suggests that HuD is a possible target molecule for antitumor immunotherapy against SCLC. We have hypothesized that anti-HuD immunity suppresses in vivo growth of HuD-expressing tumor cells. In this study, Colon 26, a murine adenocarcinoma cell line, stably transfected with the HuD gene (Colon 26/HuD cell) was used as a target cell, and the immunity against HuD was evoked by intramuscular injection of a HuD-expressing plasmid, a technique of DNA vaccination previously used in BALB/c mice. Colon 26/HuD cells were injected subcutaneously and tumor size was calculated as a product of width and length. Antitumor activity was investigated by using two different lots of Colon26/HuD cells in two protocols: Protocol 1, in which either Colon 26/HuD or Colon 26 cells were injected in each side, and Protocol 2, in which Colon 26/HuD cells alone were injected. The size of Colon 26/HuD tumors obtained from mice vaccinated with HuD-expressing plasmid was significantly smaller than those from negative control plasmid-vaccinated mice (86.6 +/- 29.9 versus 195.3 +/- 48.1 mm2, P < 0.05 in Protocol 1; 107.7 +/- 12.8 versus 156.6 +/- 22.8 mm2, P < 0.05 in Protocol 2). Moreover, the de novo DNA synthesis of spleen cells obtained from HuD-vaccinated mice was significantly enhanced. In addition, anti-HuD antibody was found in individual sera obtained from HuD-vaccinated mice. DNA vaccination with mouse HuD antigen suppressed HuD-expressing tumor growth in a murine SCLC model.
Ohwada
A
A
Departments of Respiratory Medicine and Biochemistry, Juntendo University School of Medicine, Tokyo, Japan. aohwada@med.juntendo.ac.jp
Nagaoka
I
I
Takahashi
F
F
Tominaga
S
S
Fukuchi
Y
Y
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000517:prevention & control*; D002455:Cell Division; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D005260:Female; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000627:therapeutic use*
D019496:Cancer Vaccines; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA