Identification of protamine 1 as a novel cancer-testis antigen in early chronic lymphocytic leukaemia.
Early chronic lymphocytic leukaemia (CLL) is an ideal disease for immunotherapy. We previously showed that SEMG 1 is a cancer-testis (CT) antigen in CLL. In this study, SEMG 1 was applied as the bait in a yeast two-hybrid system of a testicular cDNA library. Seven clones were isolated and Protamine (Prm) 1 was identified as a novel CT antigen in early CLL. PRM1 transcripts were detected in 11/41 (26.8%) patients. Prm 1 protein was also expressed but heterogeneously within individual patients. Of the 11 patients expressing Prm 1, four expressed Zap 70 protein and seven did not. These results, therefore, indicate that Prm 1 could potentially be a suitable target for the design of tumour vaccine for patients with early CLL, including for those with poor risk CLL. High titres of Prm 1 IgG antibodies could be detected in 20 of these 41 CLL patients but not in any of the 20 healthy donors (P = 0.0001), suggesting the presence of Prm 1-reactive immune responses within the immune repertoire of patients with early CLL. Further work is warranted, especially in approaches to upregulate Prm 1 expression, and to determine the role of Prm 1 as an immunotherapeutic target for early CLL.
Meklat
Farouk
F
Cancer Research Program, Harrington Regional Medical Center Inc, Amarillo, TX, USA.
Zhang
Yana
Y
Shahriar
Masum
M
Ahmed
Sharif U
SU
Li
Wei
W
Voukkalis
Nikolaos
N
Wang
Zhiqing
Z
Zhang
Jian
J
Mastulov
Suhkrob
S
Jewell
Andrew
A
Giannakouros
Thomas
T
Lim
Seah H
SH
D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D019496:Cancer Vaccines; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D008297:Male; D011479:Protamines / Q000032:analysis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D029607:Seminal Vesicle Secretory Proteins / Q000032:analysis; D013737:Testis / Q000276:immunology; D020798:Two-Hybrid System Techniques; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
D000906:Antibodies; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D007074:Immunoglobulin G; C082073:PRM1 protein, human; D011479:Protamines; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen; D051746:ZAP-70 Protein-Tyrosine Kinase