IDIOTYPE-CYTOKINE FUSION PROTEINS AS CANCER VACCINES - RELATIVE EFFICACY OF IL-2, IL-4, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Idiotypic determinants, antigenic sites expressed on the variable regi on of Ig molecules of malignant B cells, represent tumor-specific Ags but are weak immunogens. We have previously shown that the immunogenic ity can be dramatically increased by fusing tumor Id to granulocyte ma crophage (GM)-CSF. Here, we demonstrate that fusion proteins with IL-2 or IL-4 can also be highly immunogenic. Co-immunization of these fusi on proteins with another Id demonstrated the importance of physical li nkage between the cytokine and relevant Ag for this enhancement. All t hree fusion proteins are capable of eliciting significant levels of sp ecific Abs against the Id without the use of carrier proteins or adjuv ants, although the CM-CSF fusion protein appeared to be unique in its ability to induce higher titers of anti-Id Abs in the primary response . Furthermore, the Id-IL-2 fusion protein induced high titers of IgG2a and IgG3 anti-Id Abs, whereas the Id-IL-4 and Id-GM-CSF fusion protei ns did not. Despite the differences, tumor protection was comparable i n all mice having significant titers of anti-Id Abs, regardless of the fusion protein used. We conclude that Id-cytokine fusion proteins are potent immunogens that can elicit significant antitumor immunity. The general approach of fusing a cytokine to a potential Ag may be applic able to the design of vaccines for immunotherapy of other types of tum ors as well as for other pathogens and disease states.