Fingerprinting the circulating repertoire of antibodies from cancer patients.
Recognition of molecular diversity in disease is required for the development of targeted therapies. We have developed a screening method based on phage display to select peptides recognized by the repertoire of circulating tumor-associated antibodies. Here we isolated peptides recognized by antibodies purified from the serum of prostate cancer patients. We identified a consensus motif, NX(S/T)DK(S/T), that bound selectively to circulating antibodies from cancer patients over control antibodies from blood donors. We validated this motif by showing that positive serum reactivity to the peptide was specifically linked to disease progression and to shorter survival in a large patient population. Moreover, we identified the corresponding protein eliciting the immune response. Finally, we showed a strong and specific positive correlation between serum reactivity to the tumor antigen, development of metastatic androgen-independent disease, and shorter overall survival. Exploiting the differential humoral response to cancer through such an approach may identify molecular markers and targets for diagnostic and therapeutic intervention.
Mintz
Paul J
PJ
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Kim
Jeri
J
Do
Kim-Anh
KA
Wang
Xuemei
X
Zinner
Ralph G
RG
Cristofanilli
Massimo
M
Arap
Marco A
MA
Hong
Waun Ki
WK
Troncoso
Patricia
P
Logothetis
Christopher J
CJ
Pasqualini
Renata
R
Arap
Wadih
W
D000912:Antibodies, Neoplasm / Q000032:analysis / Q000097:blood* / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology*; D006801:Humans; D008297:Male; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology*; D018013:Receptors, Neuropeptide / Q000097:blood / Q000276:immunology; D012016:Reference Values
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C467732:GRP8 protein, human; D019151:Peptide Library; D018013:Receptors, Neuropeptide