Recent advances in multiple myeloma immunotherapy

Multiple myeloma (MM) responds to, but is not cured by, chemotherapy and may therefore be amenable to tumor-specific immunization in the setting of minimal residual disease. The idiotype of the monoclonal immunoglobulin expressed by the tumor provides a clear tumor-specific antigen. Patients with follicular lymphoma have unequivocally established that idiotypic vaccination, administered when patients have minimal residual disease, has an antitumor effect and potential to improve the clinical outcome. This result and preclinical studies demonstrating that MM cells display idiotypic peptides on their surface in a form suitable for recognition and killing by host T cells, foster the application of idiotypic vaccination in MM. The current vaccine production involves idiotype protein purification for each patient followed by conjugation to exogenous, immunogenic carriers in order to break immunological tolerance. Furthermore, recent advances in molecular cloning and development of novel antigen delivery systems are making it possible to streamline the production of equally or more effective idiotypic vaccines. Particularly, DNA vaccines utilising genetic carriers to target idiotype on dendritic cells in vivo have proven successful in preclinical models. Additional candidate T cell antigens, such as MUC1, the cancer-testis antigens, and telomerase have been identified as potential targets for immunization. The possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy is also being actively explored. Finally, clinical studies have begun in which dendritic cells are generated ex vivo, loaded with tumor antigen(s), and reinfused to immunize patients.