B-cell lymphoma idiotypes chimerized by gene targeting can induce tumor immunity

Immunization with modified immunoglobulin (Ig) idiotypes (Ids) of B-cell ly mphomas is an attractive approach of experimental tumor immunotherapy. We s how here that B-lymphoma cells can be gene-modified by homologous recombina tion at the Ig heavy chain locus. Although it has been demonstrated previou sly that a protein vaccine containing a mouse/human chimeric Ig had no immu nostimulatory effect, we show that a xenogeneic Fc segment attached to the Id by gene targeting in autologous murine tumor cells can serve as an immun ogenic carrier and is capable of inducing tumor protection. A prerequisite for successful vaccination is the delivery of tumor cells that have been en gineered to express the Id in the chimeric form rather than administration of the soluble chimeric protein. Also DNA vaccination with plasmids encodin g chimeric Ids was reported to induce an anti-idiotypic response, suggestin g that there might be related mechanisms such as enhanced antigen presentat ion. Immunization with engineered lymphoma cells is a very potent protocol: in the cell-based setting, minute levels of expression in the gene-targete d cells are sufficient to confer tumor immunity. Because the titers of anti -id antibodies induced do not reflect the degree of tumor protection, the i mmune mechanisms responsible for tumor rejection cannot be ascribed exclusi vely to a humoral response.