Document Detail

Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer.
MedLine Citation:
PMID:  22674550     Owner:  NLM     Status:  MEDLINE    
Therapeutic intravesical instillation of bacillus Calmette-Guérin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non-muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as adjuvant therapy shortly after tumor resection; however, the precise mechanisms remain unclear. Using an experimental model, we demonstrate that after a single instillation, BCG could disseminate to bladder draining lymph nodes and prime interferon-γ-producing T cells. Nonetheless, repeated instillations with live BCG were necessary for a robust T cell infiltration into the bladder. Parenteral exposure to BCG before instillation overcame this requirement; after the first intravesical instillation, BCG triggered a more robust acute inflammatory process and accelerated T cell entry into the bladder, as compared to the standard protocol. Moreover, parenteral exposure to BCG before intravesical treatment of an orthotopic tumor markedly improved response to therapy. Indeed, patients with sustained preexisting immunity to BCG showed a significant improvement in recurrence-free survival. Together, these data suggest that monitoring patients' response to purified protein derivative, and, in their absence, boosting BCG responses by parenteral exposure before intravesical treatment initiation, may be a safe and effective means of improving intravesical BCG-induced clinical responses.
Claire Biot; Cyrill A Rentsch; Joel R Gsponer; Frédéric D Birkhäuser; Hélène Jusforgues-Saklani; Fabrice Lemaître; Charlotte Auriau; Alexander Bachmann; Philippe Bousso; Caroline Demangel; Lucie Peduto; George N Thalmann; Matthew L Albert
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-07     Completed Date:  2012-10-03     Revised Date:  2012-12-03    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  137ra72     Citation Subset:  IM    
Unité d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, F-75724 Paris, France.
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MeSH Terms
Administration, Intravesical
BCG Vaccine / therapeutic use*
Flow Cytometry
Fluorescent Antibody Technique
Immunity, Innate / immunology
Immunotherapy / methods*
Mice, Inbred C57BL
T-Lymphocytes / immunology*
Urinary Bladder Neoplasms / therapy*
Reg. No./Substance:
0/BCG Vaccine
Comment In:
Eur Urol. 2012 Nov;62(5):935-6   [PMID:  23036348 ]
Nat Rev Urol. 2012 Jul;9(7):354   [PMID:  22732859 ]

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