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
| Autor: | Burkhard Kneitz, Renata Pasqualini, P. Adam, Limor Chen, Arkadius Kocot, Joachim Fensterle, Hubertus Riedmiller, Cora Reiss, Peter U. Ardelt, Elmar W. Gerharz, Wadih Arap |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment Cystectomy medicine Humans Heat-Shock Proteins Aged Aged 80 and over Carcinoma Transitional Cell Bladder cancer Urinary bladder business.industry Carcinoma in situ Cancer Combination chemotherapy Immunotherapy Middle Aged medicine.disease Antibodies Bacterial Mycobacterium bovis Transitional cell carcinoma medicine.anatomical_structure Treatment Outcome Oncology Urinary Bladder Neoplasms Immunology BCG Vaccine business Biomarkers |
| Zdroj: | Cancer. 116(3) |
| ISSN: | 0008-543X |
| Popis: | 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. Cancer 2010. © 2009 American Cancer Society. |
| Databáze: | OpenAIRE |
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