Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma.
Vaccination with the idiotype (Id) protein derived from B-cell malignancies can produce Id-specific immune responses that correlate with improved remission duration and survival rates in patients with follicular non-Hodgkin's lymphoma (NHL). A state of minimal or no residual disease correlates strongly with the laboratory detection of a cellular or humoral immune response. High-dose cytotoxic therapy (HDCT) with autologous stem cell support (autologous bone marrow transplantation [ABMT]) can provide profound cytoreduction of B-cell NHL, but the potential immune suppression associated with myeloablative therapy may compromise a patient's ability to mount a specific immune response. To determine whether patients with NHL could mount detectable immuneresponses following ABMT, Id vaccines were administered at 2 to 12 months following myeloablative therapy to a series of patients with relapsed or resistant B-cell NHL. Two different vaccination strategies produced robust immune responses against KLH in all patients, supporting the capacity of the reconstituted immune system following HDCT to react against a strong antigen. Combining the results from both vaccination strategies, 10 of 12 patients mounted Id-specific humoral or cellular responses. Vaccinations were consistently well tolerated. Of the 12 patients, 7 have experienced prolonged remissions with a follow-up from HDCT ranging from 3 to more than 11 years. Our experience serves to document the ability of the recovering immune system to react against both self and xenotypic antigens and supports the feasibility and safety of antigen-specific vaccination following myeloablative therapy in patients with B-cell NHL.
Davis
T A
TA
Division of Medical Oncology, Stanford University School of Medicine, California 94305-5306, USA.
Hsu
F J
FJ
Caspar
C B
CB
van Beckhoven
A
A
Czerwinsk
D K
DK
Liles
T M
TM
Taidi
B
B
Benike
C J
CJ
Engleman
E G
EG
Levy
R
R
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006433:Hemocyanins / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D012449:Safety; D013185:Squalene / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014611:Vaccination; D014916:Whole-Body Irradiation
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D007130:Immunoglobulin Idiotypes; D011136:Polysorbates; D011947:Receptors, Antigen, B-Cell; C077975:Syntex adjuvant formulation; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005047:Etoposide; D013185:Squalene; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D002330:Carmustine; D007069:Ifosfamide