HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response

• DOI: 10.1007/s00262-011-1087-2
• Publication Date: 2011-08-10T11:44:31Z
• Authors: Gaia Codolo; Matteo Fassan; Fabio Munari; Andrea Volpe; Piefrancesco Bassi; Massimo Rugge; Francesco Pagano; Mario Milco D’Elios; Marina de Bernard
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; Cytotoxicity; Bacterial Protein; Inbred C57BL; Cell Line; Mice; 03 medical and health sciences; Bacterial Proteins; Immunologic; Cell Line, Tumor; Animals; Humans; Tumor; Bladder cancer; HP-NAP; Immunotherapy; Th1 response; Administration, Intravesical; Animals; BCG Vaccine; Bacterial Proteins; Cell Line, Tumor; Cytotoxicity, Immunologic; Female; Helicobacter pylori; Humans; Immunotherapy; Mice; Mice, Inbred C57BL; Th1 Cells; Urinary Bladder Neoplasms; Helicobacter pylori; Intravesical; Animal; Bladder cancer; Th1 Cells; hp-nap; 3. Good health; HP-NAP; Mice, Inbred C57BL; Th1 Cell; Administration, Intravesical; Urinary Bladder Neoplasms; Th1 response; Administration; HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response.; BCG Vaccine; Female; Immunotherapy; Human

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.