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.