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

Cancer. 2010 Feb 1;116(3):600-9. doi: 10.1002/cncr.24770.


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / biosynthesis*
  • BCG Vaccine / immunology
  • BCG Vaccine / therapeutic use*
  • Biomarkers / analysis
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / therapy*
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / immunology*
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium bovis / metabolism
  • Treatment Outcome
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / therapy*


  • Antibodies, Bacterial
  • BCG Vaccine
  • Biomarkers
  • Heat-Shock Proteins
  • heat-shock protein 65, human