B-cell malignancies as a model for cancer vaccines: From prototype protein to next generation genetic chemokine fusions

B-cell malignancy-derived Ig may be considered a model tumor antigen for vaccine development. However, as a non-immunogenic self antigen, it must also be first rendered immunogenic by chemical or genetic fusion to carriers which enable the induction of protective anti-tumor immunity in murine tumor models. Our group has demonstrated that active immunizations of human patients with idiotypic vaccines elicited antigen-specific CD8⁺ T-cell responses and antitumor effects. Several alternative preclinical strategies to develop vaccines have been previously reported, including fusion of tumor idiotype-derived single chain Fv with cytokines and immunogenic peptides. On the other hand, we have recently explored a different approach in which the model antigen is rendered immunogenic in mice by genetically fusing it to a chemokine moiety. Administration of these vaccines as fusion proteins or naked DNA vaccines may allow efficient targeting of antigen-presenting cells in vivo. Potent anti-tumor immunity was dependent on the generation of specific anti-idiotypic antibodies and both CD4⁺ and CD8⁺ effector T cells. We propose that chemokine fusion may represent a novel, general strategy for formulating existing or newly identified tumor and HIV antigens into vaccines for cancer and AIDS, respectively, which elicit potent CD8⁺ T-cell immunity.