Reactive antibodies against bacillus Calmette-Guerin heat-shock protein-65 potentially predict the outcome of immunotherapy for high-grade transitional cell carcinoma of the bladder.
BACKGROUND
Intravesical immunotherapy with Mycobacterium bovis (M. bovis) bacillus Calmette-Guerin (BCG) is the current standard of care against superficial, high-grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle-invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG-induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy.


METHODS
Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s).


RESULTS
An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat-shock protein 65 (HSP-65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti-HSP-65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients.


CONCLUSIONS
The current results indicated that antibody production against M. bovis BCG HSP-65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG-based treatment for individual patients with bladder cancer.
Ardelt
Peter U
PU
Department of Urology and Pediatric Urology, Bavarian Julius Maximilians-University Medical School, Wurzburg, Germany. ardelt_p@klinik.uni-wuerzburg.de
Kneitz
Burkhard
B
Adam
Patrick
P
Reiss
Cora
C
Kocot
Arkadius
A
Fensterle
Joachim
J
Chen
Limor
L
Pasqualini
Renata
R
Arap
Wadih
W
Gerharz
Elmar W
EW
Riedmiller
Hubertus
H
D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001500:BCG Vaccine / Q000276:immunology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000378:metabolism; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D015415:Biomarkers; D006360:Heat-Shock Proteins; C060293:HSPD1 protein, human; D018834:Chaperonin 60; D024101:Mitochondrial Proteins