Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia.
To design a specific immunotherapy for leukemia patients, the identification of leukemia-associated antigens (LAAs) is a pivotal step. Antileukemic effects after hematopoetic stem cell transplantation for myeloid leukemias are observed and might be related to the recognition of LAAs. Using the serological screening of an expression library (SEREX) of K562 cells, we identified 16 different clones encoding LAAs eliciting a humoral immune response, among them the heat shock proteins HSJ2 and HSP70, the M-phase phosphoprotein 11 (MPP11), the BRCA1-associated protein (BRAP), the Jkappa recombination binding protein (RBPJkappa) and the receptor for hyaluronic acid mediated motility (RHAMM). Serological responses to MPP11 were observed in 7/19 (37%) of patients with acute myeloid leukemia (AML) and 6/16 (38%) of patients with chronic myeloid leukemia (CML), but not in healthy volunteers (0/20). IgG antibodies directed against MPP11 were also detected in 25-50% of the sera of patients with solid tumors such as melanoma, renal cell, ovarian and breast carcinoma. mRNA expression of MPP11 was detected in 20/20 AML patients and 7/10 patients with CML. In normal tissues, strong mRNA expression of MPP11 was only detected in testis. By real-time PCR, we detected upregulation of MPP11 in leukemic blasts. Simultaneous humoral immune responses to 2 or more of the 16 LAAs identified here was observed, suggesting the feasibility of a polyvalent vaccination as an option for immunotherapies in leukemia patients.
Greiner
Jochen
J
Third Department of Internal Medicine, University of Ulm, Ulm, Germany.
Ringhoffer
Mark
M
Taniguchi
Masanori
M
Hauser
Thomas
T
Schmitt
Anita
A
Döhner
Hartmut
H
Schmitt
Michael
M
D000208:Acute Disease; D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000032:analysis*; D015513:Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000556:secondary
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins