Epitope recognition by anti-cathepsin D autoantibodies in endometrial cancer patients.
OBJECTIVE
This study analyzed a model for the identification of specific epitopes recognized by autologous tumor-reactive humoral responses of endometrial cancer patients as potential markers for the monitoring of cancer.


METHODS
The presence of circulating pro- and mature forms of cathepsin D and antibodies reactive with this enzyme were identified by Western immunoblot and quantitated by an enzyme immunoassay. Specific immunoreactivities with 34- and 52-kDa cathepsin D forms were analyzed by Western immunoblot using sera from endometrial cancer patients (n = 40) and normal volunteers (n = 15). Subsequently, reactivities with specific cathepsin D epitopes were defined by a peptide-specific ELISA.


RESULTS
Circulating pro-forms of cathepsin D were detected in 31 of 40 endometrial cancer patients tested and none of the control volunteers. Circulating IgG reactive with cathepsin D could be demonstrated in 29/31 patients with circulating procathepsin D, while an anti-cathepsin D response was not detectable in normal controls. This response appeared to be directed against the pro-peptide portion of cathepsin D. Using a peptide-specific ELISA, the frequencies of antibody production against specific epitopes within the pro-peptide were defined.


CONCLUSIONS
There is a demonstrable tumor-reactive immune response elicited in endometrial cancer patients, directed against specific antigenic epitopes, some of which are conserved among these patients. Since these proteins are recognized as non-self, due at least in part to posttranslational processing errors, defining these epitopes will be useful as a means of diagnosis, assessment of therapeutic success, and, ultimately, identification of immunotherapeutic targets.
Bosscher
J R
JR
Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Gerçel-Taylor
C
C
Watkins
C S
CS
Taylor
D D
DD
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002402:Cathepsin D / Q000097:blood / Q000276:immunology*; D016889:Endometrial Neoplasms / Q000097:blood / Q000276:immunology*; D004792:Enzyme Precursors / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008969:Molecular Sequence Data
D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D004792:Enzyme Precursors; D000939:Epitopes; D007074:Immunoglobulin G; C058345:procathepsin D; D002402:Cathepsin D