Translational development of active immunotherapy for hematologic malignancies

The B-cell tumor-derived Ig receptor may be considered a model tumor antigen for cancer vaccine development. However, as a non-immunogenic, self-antigen, it also must be first rendered immunogenic by chemical or genetic fusion to carriers which enable the induction of protective antitumor immunity in experimental tumor models. Our group has demonstrated that active immunization of human patients with idiotypic protein vaccines containing soluble GM-CSF elicited antigen specific CD8⁺ T cell responses and antitumor effects. An alternative strategy to develop vaccines is the genetic fusion of tumor idiotype-derived single chain antigen with a chemokine moiety. Administration of these vaccines as fusion proteins or naked DNA vaccines may allow more efficient targeting of antigen presenting cells in vivo. Potent antitumor immunity was elicited in mice which was dependent on the generation of specific 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.