Treatments with cancer-vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T-cells in the bladder and tumor-regression in murine bladder-cancer models. Here we determined whether an adjuvanted cancer-vaccine can be safely administered with concomitant standard intravesical Bacilus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle-invasive bladder cancer (NMIBC).
In a non-randomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer-vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine-injections or BCG-instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG-instillations.
The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AE were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T-cells were induced in blood, irrespective of BCG treatment. Interestingly, such T-cells were only detected in urine upon BCG-induced T-cell infiltration.
Cancer-vaccines including strong adjuvants can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T-cells in the bladder upon BCG provides proof principle evidence that cancer-vaccines with local immunostimulation may be beneficial.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Aug 12 [Epub ahead of print]
Laurent Derré, Valérie Cesson, Ilaria Lucca, Yannick Cerantola, Massimo Valerio, Urs Fritschi, Yannis Vlamopoulos, Rodolfo Burruni, Anne-Sophie Legris, Florence Dartiguenave, Dalila Gharbi, Virginie Martin, Laurent Vaucher, Daniel E Speiser, Pedro Romero, Patrice Jichlinski, Denise Nardelli-Haefliger
Urology Research Unit - Urology Department, University Hospital Center and University of Lausanne., Dpt Urology, Centre Hospitalier Universitaire Vaudois and University of Lausanne., Clinical Tumor Biology & Immunotherapy Group, Department of Oncology, Ludwig Cancer Research Center, University of Lausanne., Ludwig Center for Cancer Research of the University of Lausanne, University of Lausanne., Dpt of Urology, Centre Hospitalier Universitaire Vaudois and University of Lausanne., Dpt of Urology, Centre Hospitalier Universitaire Vaudois and University of Lausanne .