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Am. J. Respir. Cell Mol. Biol., Volume 21, Number 1, July, 1999 37-43

DNA Vaccination against HuD Antigen Elicits Antitumor Activity in a Small-Cell Lung Cancer Murine Model

Akihiko Ohwada, Isao Nagaoka, Fumiyuki Takahashi, Shigeru Tominaga, and Yoshinosuke Fukuchi

Departments of Respiratory Medicine and Biochemistry, Juntendo University School of Medicine, Tokyo, Japan

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.




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