CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia.
This report describes a tumor-associated antigen, termed CML66, initially cloned from a chronic myelogenous leukemia (CML) cDNA expression library. CML66 encodes a 583-aa protein with a molecular mass of 66 kDa and no significant homology to other known genes. CML66 gene is localized to human chromosome 8q23, but the function of this gene is unknown. CML66 is expressed in leukemias and a variety of solid tumor cell lines. When examined by Northern blot, expression in normal tissues was restricted to testis and heart, and no expression was found in hematopoietic tissues. When examined by quantitative reverse transcription-PCR, expression in CML cells was 1.5-fold higher than in normal peripheral blood mononuclear cells. The presence of CML66-specific antibody in patient serum was confirmed by Western blot and the development of high titer IgG antibody specific for CML66 correlated with immune induced remission of CML in a patient who received infusion of normal donor lymphocytes for treatment of relapse. CML66 antibody also was found in sera from 18-38% of patients with lung cancer, melanoma, and prostate cancer. These findings suggest that CML66 may be immunogenic in a wide variety of malignancies and may be a target for antigen-specific immunotherapy.
Yang
X F
XF
Center for Hematologic Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Wu
C J
CJ
McLaughlin
S
S
Chillemi
A
A
Wang
K S
KS
Canning
C
C
Alyea
E P
EP
Kantoff
P
P
Soiffer
R J
RJ
Dranoff
G
G
Ritz
J
J
D019943:Amino Acid Substitution; D000912:Antibodies, Neoplasm / Q000097:blood*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009928:Organ Specificity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; C431278:NUDCD1 protein, human