Evaluation of antitumor immunity and paraneoplastic neurological syndrome evoked by murine dendritic cells pulsed with HuD antigen.

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There is a clinically significant correlation between the presence of an antibody against the paraneoplastic encephalomyelitis antigen HuD (HuD antigen) and limitation of tumor spread in patients with small cell lung cancer (SCLC). The dendritic cells pulsed with tumor specific antigen such as HuD antigen will potentate the cellular immunity against the tumors. The expression of HuD antigen was evaluated by Western blotting in the murine splenic dendritic cells infected with HuD antigen expressing adenovirus vector. However, the expression of HuD antigen was not detectable by western blotting in the cells infected with our HuD-expressing adenovirus vector even at 50 moi (multiplicity of infection). Next we evaluated the effects of granulysin, a tumorcidal molecule secreted by cytotoxic T cells (CTL) and natural killer (NK) cells in HuD antigen-expressing small cell lung cancer murine model cells (Colon 26/HuD) infected with granulysin expressing adenovirus vector. Adenovirus vector-mediated transfer of 9kDa granulysin increased DNA fragmentation in Colon 26/HuD cells 2.5-fold and suppressed 21% of the Colon 26/HuD proliferation on day 3 (p<0.05 for each value) after the transfer of granulysin, compared with the control adenovirus vector transfer. In contract, adenovirus vector-mediated transfer of 9kDa granulysin did not increase DNA fragmentation nor suppress the proliferation of Colon 26 parent cells. The sensitivity of HuD-expressing tumor cells to granulysin is likely to partially explain the susceptibility of SCLC to cell-mediated immunity. These results support that HuD antigen is still good candidate molecule for antitumor immunity against SCLC and propose to evaluate the anti-tumor effect of dendritic cells pulsed with recombinant HuD antigen.