Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients.

Abstract

PURPOSE:

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 Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle-invasive bladder cancer (NMIBC).

EXPERIMENTAL DESIGN:

In a nonrandomized 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.

RESULTS:

The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs 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.

CONCLUSIONS:

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-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717-25. ©2016 AACR.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 3 Pg. 717-725 (Feb 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 27521445 (Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• BCG Vaccine
• Cancer Vaccines
• Cytokines
• Lipid A
• MAGEA3 protein, human
• Neoplasm Proteins
• Oligodeoxyribonucleotides
• Plant Extracts
• ProMune
• Recombinant Proteins
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (administration & dosage)
• Administration, Intravesical
• Antigens, Neoplasm (immunology)
• BCG Vaccine (administration & dosage, adverse effects, therapeutic use)
• Cancer Vaccines (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Transitional Cell (immunology, pathology, surgery, therapy)
• Combined Modality Therapy
• Cystectomy (methods)
• Cytokines (urine)
• Dose-Response Relationship, Immunologic
• Humans
• Immunization Schedule
• Immunotherapy (methods)
• Injections, Intramuscular
• Lipid A (administration & dosage, analogs & derivatives)
• Lymphocytes, Tumor-Infiltrating (drug effects)
• Neoplasm Proteins (immunology)
• Oligodeoxyribonucleotides (administration & dosage)
• Plant Extracts (administration & dosage)
• Quillaja
• Recombinant Proteins (immunology)
• Urinary Bladder Neoplasms (immunology, pathology, surgery, therapy)