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

Détails

ID Serval
serval:BIB_7E871163C3ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients.
Périodique
Clinical cancer research
Auteur(s)
Derré L., Cesson V., Lucca I., Cerantola Y., Valerio M., Fritschi U., Vlamopoulos Y., Burruni R., Legris A.S., Dartiguenave F., Gharbi D., Martin V., Vaucher L., Speiser D.E., Romero P., Jichlinski P., Nardelli-Haefliger D.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Statut éditorial
Publié
Date de publication
01/02/2017
Peer-reviewed
Oui
Volume
23
Numéro
3
Pages
717-725
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Comparative Study ; Journal Article
Publication Status: ppublish
Résumé
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).
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.
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.
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.

Mots-clé
Adjuvants, Immunologic/administration & dosage, Administration, Intravesical, Antigens, Neoplasm/immunology, BCG Vaccine/administration & dosage, BCG Vaccine/adverse effects, BCG Vaccine/therapeutic use, Cancer Vaccines/administration & dosage, Cancer Vaccines/adverse effects, Cancer Vaccines/therapeutic use, Carcinoma, Transitional Cell/immunology, Carcinoma, Transitional Cell/pathology, Carcinoma, Transitional Cell/surgery, Carcinoma, Transitional Cell/therapy, Combined Modality Therapy, Cystectomy/methods, Cytokines/urine, Dose-Response Relationship, Immunologic, Humans, Immunization Schedule, Immunotherapy/methods, Injections, Intramuscular, Lipid A/administration & dosage, Lipid A/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, Urinary Bladder Neoplasms/pathology, Urinary Bladder Neoplasms/surgery, Urinary Bladder Neoplasms/therapy
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/09/2016 20:22
Dernière modification de la notice
20/08/2019 14:39
Données d'usage