Paris June 6, 2012

Bladder cancer treatment with BCG may be improved with new patient protocol

Researchers from the Institut Pasteur, INSERM, Paris Descartes University and the MINES ParisTech graduate school have recently discovered a way to reinforce the effectiveness of BCG in the treatment of bladder cancer. BCG has been the standard treatment for bladder cancer tumors with a high risk of recurrence for the past 35 years. If the efficacy of this new therapeutic protocol is confirmed it would limit relapse of one of the most common cancers in industrialized countries. This work is being published today on the website of the journal Science Translational Medicine.

Even today, despite advances made in immunology, very few immunotherapy treatments (used to stimulate the immune system) have shown any clinical benefit. One notable exception has been that of bladder cancer treated with BCG, or Bacillus Calmette-Guérin, which is more widely known as the vaccine against tuberculosis. This successful “BCG therapy” simply consists of repeated localized injections of BCG to the bladder. Patient survival rate varies between 50 and 70%.

A study conducted by Claire Biot, a member of the research team working under Matthew Albert*, head of the Dendritic Cell Immunobiology Unit (Institut Pasteur/INSERM/Paris Descartes University) used mouse models to characterize the dynamics of the bladder’s immune response to BCG. This study showed that the antitumoral response improved when a simple sub-cutaneous injection of BCG preceded standard protocol “BCG therapy”; the result being that a large number of immune cells are functional with the first BCG instillation to the bladder.

In light of these results in mice, the researchers began to wonder if patients who received BCG vaccinations as children responded better to the standard treatment than patients who had not been vaccinated. Their question was answered thanks to a study conducted by the University of Bern in Switzerland where the response to treatment in two groups of patients who had been vaccinated in their childhood was compared. One group of patients still tested positive for BCG (proving the vaccine’s continued effectiveness) and the other group of patients had test results showing that the vaccine was no longer effective. The study found that over a five-year period 80% of the patients with positive test results survived the cancer without recurrence compared to just 45% of the patients who tested negative for BCG. The result is consistent with the experimental data obtained in mouse models.

This research is encouraging as it suggests that a simple intradermal injection of BCG before proceeding with the standard protocol could improve a patient's response to treatment. A clinical trial of this new therapeutic strategy should be conducted soon in order to confirm the researchers’ findings and offer improved patient care.

This research was possible thanks to financial support from the French Cancer League and the French National Cancer Institute as well as the generosity of the Caisse de retraite et de prévoyance des clercs et employés de notaires and the Swiss National Foundation.

* Matthew Albert is an INSERM research director and professor at the Institut Pasteur where he heads the Department of Immunology and directs the Dendritic Cell Immunobiology Unit (joint Institut Pasteur/INSERM Unit 818). Matthew Albert is also affiliated with Paris Descartes University.
Team member Claire Biot, a researcher from the MINES ParisTech graduate school, is assigned to the unit headed by Matthew Alber

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Pre-existing BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer, Science Translational Medicine, en ligne le 6 juin 2012
Claire Biot1,2,3, Cyrill A. Rentsch1,2,4*, Joel R. Gsponer1,2,4*, Frédéric D. Birkhäuser5, Hélène Jusforgues-Saklani1,2, Fabrice Lemaître6,7, Charlotte Auriau1,2, Alexander Bachmann5, Philippe Bousso6,7, Caroline Demangel8, Lucie Peduto9, George N. Thalmann5, Matthew L. Albert1,2,10

1 Unité d’Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, F-75724 Paris, France.
2 INSERM U818, F-75654 Paris, France.
3 Mines ParisTech, F-75272 Paris, France.
4 Department of Urology, University Hospital of Basel, CH-4031 Basel, Switzerland.
5 Department of Urology, University of Bern, Inselspital, CH-3010 Bern, Switzerland.
6 Unité des Dynamique des Réponses Immunes, Department of Immunology, Institut Pasteur, F-75724 Paris, France.
7 INSERM U668, F-75654 Paris, France.
8 Unité d’Immunobiologie de l’Infection, Department of Immunology, Institut Pasteur, F-75724 Paris, France.
9 Unité de Développement des Tissus Lymphoïdes, Department of Immunology, Institut Pasteur, F-75724 Paris, France.
10 Université Paris Descartes, F-75270 Paris, France.
* These authors contributed equally to this work.


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