The idiotype (Id) determinant on the multiple myeloma (MM) protein can be regarded as a tumor-specific marker. Immunotherapy directed at the MM Id may stem the progression of this disease. We report here on the first 12 MM patients treated at our institution with high-dose therapy and peripheral blood stem cell transplantation (PBSCT) followed by Id immunizations. MM patients received PBSCT to eradicate the majority of the disease. PBSCT produced a complete response in 2 patients, a partial response in 9 patients and stable disease in 1 patient. Three to 7 months after high-dose therapy, patients received a series of monthly immunizations that consisted of two intravenous infusions of Id-pulsed autologous dendritic cells (DC) followed by five subcutaneous boosts of Id/keyhole limpet hemocyanin (KLH) administered with adjuvant. Between 1 and 11 x 10(6) DC were obtained by leukapheresis in all patients even after PBSCT. The administration of Id-pulsed DC and Id/KLH vaccines were well tolerated with patients experiencing only minor and transient side effects. Two of 12 patients developed an Id-specific, cellular proliferative immune response and one of three patients studied developed a transient but Id-specific cytotoxic T-cell (CTL) response. Eleven of the 12 patients generated strong KLH-specific cellular proliferative immune responses showing the patients' immunocompetence at the time of vaccination. The two patients who developed a cellular Id-specific immune response remain in complete remission. Of the 12 treated patients, 9 are currently alive after autologous transplantation with a minimum follow-up of 16 months, 2 patients died because of recurrent MM and 1 patient succumbed to acute leukemia. These studies show that patients make strong anti-KLH responses despite recent high-dose therapy and that DC-based Id vaccination is feasible after PBSCT and can induce Id-specific T-cell responses. Further vaccine development is necessary to increase the proportion of patients that make Id-specific immune responses, The clinical benefits of Id vaccination in MM remain to be determined. (C) 1999 by The American Society of Hematology.
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Isshiki, Ikuko
Okamoto, Shinichiro
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Okamoto, Shinichiro
Kakimoto, Tsunenori
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Kakimoto, Tsunenori
Chen, Chien-Kang
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Chen, Chien-Kang
Mori, Takehiko
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Mori, Takehiko
Yokoyama, Kenji
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan
Yokoyama, Kenji
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Hattori, Yutaka
Ikeda, Yasuo
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Keio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, JapanKeio Univ, Sch Med, Dept Med, Div Hematol,Shinjuku Ku, Tokyo 1608582, Japan