title: Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?
abstract: Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.
authors.affiliation: Department of Urology, Eberhard-Karls University, Tuebingen, Germany.
authors.forename: Omar
authors.initials: O
authors.lastname: Fahmy
authors.affiliation: Department of Urology, University Putra Malaysia (UPM), Selangor, Malaysia.
authors.forename: Mohd Ghani
authors.initials: MG
authors.lastname: Khairul-Asri
authors.affiliation: Department of Urology, Eberhard-Karls University, Tuebingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, Eberhard-Karls University, Tuebingen, Germany. Electronic address: georgios.gakis@med.uni-tuebingen.de.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000283:Administration, Intravesical; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000737:chemistry; D001500:BCG Vaccine / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015653:Cystectomy / Q000379:methods; D018450:Disease Progression; D004357:Drug Synergism; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D008221:Lymphoid Tissue / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011788:Quality of Life; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human