Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2.
HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression in various human neoplasms. To search for HLA-A*0201 restricted peptides that induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with high binding affinity for HLA-A*0201, which has a prevalence of 40% in the Caucasian population. Of the three peptides, p41-49 and p103-111 but not p167-175 had been shown to be processed by the proteasome. Only stimulation with p103-111 induced HOM-MEL-40-specific CTLs in 5/7 patients with HOM-MEL-40/SSX2 positive breast cancers and in 6/11 healthy controls. HLA-A*0201 restriction of p103-111 was demonstrated by blocking with specific antibodies. The natural processing and presentation of p103-111 was demonstrated by the recognition of the HOM-MEL-40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM-MEL-40/SSX2 by p103-111 specific CD8+ cells. No correlation was found between CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers in the serum of patients, suggesting that CD8+ and B-cell responses against HOM-MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.
Wagner
Claudia
C
Med. Klinik I, Saarland University Medical School, D-66424 Homburg, Germany.
Neumann
Frank
F
Kubuschok
Boris
B
Regitz
Evi
E
Mischo
Axel
A
Stevanovic
Stefan
S
Friedrich
Michael
M
Schmidt
Werner
W
Rammensee
Hans-Georg
HG
Pfreundschuh
Michael
M
D000368:Aged; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D011237:Predictive Value of Tests; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D013736:Testicular Neoplasms / Q000235:genetics / Q000276:immunology*; D014162:Transfection
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins