Idiotype vaccination using dendritic cells after autologous peripheral blood progenitor cell transplantation for multiple myeloma.
The idiotype (Id) determinants on the multiple myeloma immunoglobulin can serve as tumor-specific antigens. An anti-Id immune response may stem the growth of the malignant clone. We report on 26 patients treated at our institution with high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) and vaccinated with the Id protein. The patients received chemotherapy and PBPCT to establish a minimal residual disease state. After high-dose therapy, the patients received a series of monthly immunizations consisting of 2 intravenous infusions of dendritic cells (DCs) pulsed with either Id protein or Id coupled with keyhole limpet hemocyanin (KLH) as an immunogenic carrier protein, followed by subcutaneous boosts of Id-KLH conjugates. DCs were obtained in all patients from a leukapheresis product 3 to 9 months after PBPCT. Patients were observed for toxicity, immune responses, and tumor status. The DC infusions and the administration of Id-KLH boosts were well tolerated, with patients experiencing only minor and transient side effects. Of the patients, 24 of 26 generated a KLH-specific cellular proliferative immune response. Only 4 patients developed an Id-specific proliferative immune response. Three of these immune responders were in complete remission at the time of vaccination. A total of 17 patients are alive at a median follow-up of 30 months after transplantation. Id vaccination with autologous DCs is feasible for myeloma patients after transplantation. Id-specific cellular responses can be induced in patients who are in complete remission. Further studies are needed to increase the rate of anti-Id immune responses in patients who do not achieve complete remission.
Liso
A
A
Division of Oncology, Stanford University Medical Center, California 94305-5151, USA.
Stockerl-Goldstein
K E
KE
Auffermann-Gretzinger
S
S
Benike
C J
CJ
Reichardt
V
V
van Beckhoven
A
A
Rajapaksa
R
R
Engleman
E G
EG
Blume
K G
KG
Levy
R
R
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000276:immunology; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D014182:Transplantation, Autologous; D014611:Vaccination
D007130:Immunoglobulin Idiotypes