Dossier: Myeloma Recent advances in multiple myeloma immunotherapy P.A. Ruffini 1 *, A. Biragyn, L.W. Kwak Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA (Received 18 February 2002; accepted 20 February 2002) Summary – Multiple myeloma (MM) responds to, but is not cured by, chemotherapy and may there- fore be amenable to tumor-specific immunization in the setting of minimal residual disease. The idio- type of the monoclonal immunoglobulin expressed by the tumor provides a clear tumor-specific anti- gen. 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 den- dritic cells are generated ex vivo, loaded with tumor antigen(s), and reinfused to immunize patients. © 2002 Éditions scientifiques et médicales Elsevier SAS idiotype / multiple myeloma / tumor-specific immunotherapy Current medical treatment for multiple myeloma (MM) provides only temporary remission. One actively investigated strategy to increase survival is tumor-specific activation of the immune system via antigen-specific or whole tumor cell immunization. In the last few years important progress has been made in this field leading to the point where this strat- egy is being tested in patients. This article focuses on relevant clinical and preclinical results recently achieved in the development of therapeutic vaccines and cellular therapy for MM. ANTIGEN-SPECIFIC IMMUNIZATION STRATEGIES Idiotype Multiple myeloma (MM) is a clonal B cell malig- nancy, therefore the idiotype (Id) of the immunoglo- bulin expressed by the neoplastic B cell clone rep- resents a truly tumor-specific antigen. In MM the little amount of Id on the tumor cell surface and the *Correspondence and reprints: National Cancer Institute, PO box B, Bldg 567, Rm 207, Frederick MD 21702-1201, USA. E-mail address: pruffini@mail.ncifcrf.gov (P.A. Ruffini). 1 On leave of absence from the Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca’Granda, Milan, Italy Biomed Pharmacother 2002 ; 56 : 129-32 © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved S0753332202001695/FLA