Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for tumor protection

Vaccination with immunogenic formulations of lymphoma-derived immunoglobuli n can elicit strong anti-idiotypic immune responses which have proved effec tive in murine B cell tumor challenge experiments and suggested possible be nefits in recent human clinical trials. Naked plasmid DNA vaccines encoding the Id determinants as scFv fragments provide the most promising alternati ve to protein immunization. With this approach the addition of an immunogen ic domain linked to the scFv has proved essential for the induction of a pr otective immune response. In this study we have produced a scFv gene constr uct linked to the CH3 exon of the human IgG1 constant region and tested its efficacy in inducing protective immunity against the mouse BCL1 lymphoma. We have also generated a second construct in which the BCL1 VL gene was del eted to investigate whether the VH region domain contains sufficient antige nic determinants for a protective immune response. Both constructs induced anti-idiotypic antibodies that specifically reacted with the BCL1 IgM prote in in ELISA and with BCL1 tumor cells in flow cytometry assays. Protection against tumor challenge was fully achieved with the complete scFv construct whereas immunization with the construct lacking the VL gene resulted in on ly a slight prolongation of the survival. We therefore conclude that a plas mid DNA vaccine containing the VH and VL genes of the lymphoma Ig linked to the human IgG1 CH3 exon is highly effective in inducing a protective immun e response in the BCL1 model. We also demonstrated that VH gene immunizatio n can induce strong antiidiotypic antibody responses.