An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients.
To gain insight into the mechanisms of molecular recognition and humoral immune response in ovarian cancer, we used fingerprinting, a phage display-based combinatorial selection to isolate peptide ligands to tumor-related antibodies present in ascites from patients with advanced disease. First, we have isolated a consensus motif (sequence CVPELGHEC) in 86% of the peptides screened; this enriched motif was selected from a total of 10(8)-10(9) unique random sequences present in the library. Next, we identified the heat-shock protein 90 kDa (HSP90) as the native antigen mimicked by the motif. Finally, we evaluated the expression of HSP90 and the presence of antibodies against the HSP90-mimic peptide in a large panel of ovarian cancer patients and controls. In tissue microarrays, we show that the expression of HSP90 is ubiquitous. However, the corresponding humoral immune response against HSP90 is restricted to a subset of patients with stage IV disease. Together, these results show that screening humoral response can identify tumor antigens that may serve as molecular targets in ovarian cancer. Recognition of such relevant proteins in the immunobiology of malignant tumors may lead to the development of therapies
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Claudia I
CI
Vidal
Paul J
PJ
Mintz
Karen
K
Lu
Lee M
LM
Ellis
Luigi
L
Manenti
Raffaella
R
Giavazzi
David M
DM
Gershenson
Russell
R
Broaddus
Jinsong
J
Liu
Wadih
W
Arap
Renata
R
Pasqualini
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000906:Antibodies; D000941:Antigens / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000737:chemistry; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007107:Immune System; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D011379:Prognosis; D011994:Recombinant Proteins / Q000737:chemistry
D000906:Antibodies; D000941:Antigens; D000951:Antigens, Neoplasm; D018841:HSP90 Heat-Shock Proteins; D007074:Immunoglobulin G; D019151:Peptide Library; D010455:Peptides; D011994:Recombinant Proteins; D005982:Glutathione Transferase