Induction of tumor immunity by autologous B lymphoma cells expressing a genetically engineered idiotype

A fusion protein containing a B cell lymphoma idiotype (Id) and granulocyte -macrophage colony-stimulating factor (GIW-CSF) is a potent stimulator of t umor immunity. In three different tumor models we show that immunization wi th autologous lymphoma cells that have been engineered to express the Id in the context of GlW-CSF is much more effective than immunization with an eq uivalent dose of the purified protein. The lymphoma Id could be modified by I introducing the GM-CSF gene into the immunoglobulin (Ig) heavy chain loc us via gene targeting. This approach circumvents the isolation of the rearr anged immunoglobulin variable genes from the tumor and the preparation of t umor-specific vector constructs. The low production of Id/GM-CSF fusion pro teins by transfected cells, which is a major obstacle in the use of purifie d fusion proteins for immunotherapy, is due to the presence of the cytokine gene in the immunoglobulin locus. Low production, however, is not limiting in the cell-based setting, because upon in vivo administration of the modi fied autologous cells, even minute expression levels are sufficient to indu ce tumor immunity.