title: HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response.
abstract: Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant. Furthermore, non-responder patients are candidate to radical cystectomy in the absence of valuable alternative options. These aspects have prompted the search for newer biological response modifiers (BRM) with a better benefit/side effects ratio. The toll-like receptor (TLR) 2 ligand, Helicobacter pylori protein HP-NAP, has been shown to deserve a potential role as BRM. HP-NAP is capable of driving the differentiation of T helper (Th) 1 cells, both in vitro and in vivo, because of its ability to create an IL-12-enriched milieu. Herein, we report that local administration of HP-NAP decreases tumour growth by triggering tumour necrosis in a mouse model of bladder cancer implant. The effect is accompanied by a significant accumulation of both CD4+ and CD8+ IFN-γ-secreting cells, within tumour and regional lymph nodes. Noteworthy, HP-NAP-treated tumours show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Our findings strongly indicate that HP-NAP might become a novel therapeutic "bullet" for the cure of bladder tumours.
authors.affiliation: Department of Biology, University of Padua, Via U. Bassi 58/B, 35121 Padua, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Codolo
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Fabio
authors.initials: F
authors.lastname: Munari
authors.forename: Andrea
authors.initials: A
authors.lastname: Volpe
authors.forename: Piefrancesco
authors.initials: P
authors.lastname: Bassi
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Francesco
authors.initials: F
authors.lastname: Pagano
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: D001500:BCG Vaccine; D001426:Bacterial Proteins