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

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.

Author information

1
Department of Urology and Pediatric Urology, Bavarian Julius Maximilians-University Medical School, Wurzburg, Germany. ardelt_p@klinik.uni-wuerzburg.de

Abstract

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.

PMID:
19957324
DOI:
10.1002/cncr.24770
[Indexed for MEDLINE]
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