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

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
DOI: 10.1007/s00262-011-1087-2 Publication Date: 2011-08-10T11:44:31Z
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.
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