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 an tibody against the paraneoplastic encephalomyelitis antigen HuD and the lim itation of tumor spread in patients with small-cell lung cancer (SCLC). Thi s suggests that HuD is a possible target molecule for antitumor immunothera py against SCLC. We have hypothesized that anti-HuD immunity suppresses ill vivo growth of HuD-expressing tumor cells. In this study, Colon 26, a muri ne 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 evok ed by intramuscular injection of a HuD-expressing plasmid, a technique of D NA vaccination previously used in BALB/c mice. Colon 26/HuD cells were inje cted 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/H uD or Colon 26 cells were injected in each side, and Protocol 2, in which C olon 26/HuD cells alone were injected. The size of Colon 26/HuD tumors obta ined from mice vaccinated with HuD-expressing plasmid was significantly sma ller than those from negative control plasmid-vaccinated mice (86.6 +/- 29. 9 versus 195.3 +/- 48.1 mm(2), P < 0.05 in Protocol 1; 107.7 +/- 12.8 versu s 156.6 +/- 22.8 mm(2), P < 0.05 in Protocol 2). Moreover, the de novo DNA synthesis of spleen cells obtained from HuD-vaccinated mice was significant ly enhanced. In addition, anti-HuD antibody was found in individual sera ob tained from HuD-vaccinated mice. DNA vaccination with mouse HuD antigen sup pressed HuD-expressing tumor growth in a murine SCLC model.