Cancer Immunology, Immunotherapy

, Volume 61, Issue 1, pp 31–40 | Cite as

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

  • Gaia Codolo
  • Matteo Fassan
  • Fabio Munari
  • Andrea Volpe
  • Piefrancesco Bassi
  • Massimo Rugge
  • Francesco Pagano
  • Mario Milco D’Elios
  • Marina de Bernard
Original article


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.


Bladder cancer HP-NAP Immunotherapy Th1 response 



This work was supported by Progetto di Eccellenza Fondazione Cassa di Risparmio di Padova e Rovigo, Research Grant from the University of Padua (CPDA074121/07); Associazione Italiana per la Ricerca sul Cancro, Grant Regionale 2008, to M.d.B. and M.R. “Guido Berlucchi” Foundation, and “Morgagni” Association for Oncological Research (Padua) to M.R. European Union FP7 NOPERSIST research grant on tuberculosis, and Italian Ministry of Health research grant on tuberculosis to M.M.D.E. We thank V. Bronte for valuable discussions and C. Montecucco for critical reading of the manuscript.

Conflict of interest

M.M.D.E and M.d.B. are within the applicants of EU Patent 05425666.4 for HP-NAP as a potential therapeutic agent in cancer, allergic and infectious diseases. The remaining authors declare that no conflict of interest exists.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Gaia Codolo
    • 1
    • 2
  • Matteo Fassan
    • 3
  • Fabio Munari
    • 2
    • 4
  • Andrea Volpe
    • 5
  • Piefrancesco Bassi
    • 5
  • Massimo Rugge
    • 3
    • 6
  • Francesco Pagano
    • 2
  • Mario Milco D’Elios
    • 7
  • Marina de Bernard
    • 1
    • 2
  1. 1.Department of BiologyUniversity of PaduaPaduaItaly
  2. 2.Venetian Institute of Molecular MedicinePaduaItaly
  3. 3.Department of Medical Diagnostic Sciences and Special Therapies Surgical Pathology and Cytopathology UnitUniversity of PaduaPaduaItaly
  4. 4.Department of Biomedical SciencesUniversity of PaduaPaduaItaly
  5. 5.Department of UrologyThe Catholic University School of MedicineRomeItaly
  6. 6.Istituto Oncologico del Veneto IOV-IRCCSPaduaItaly
  7. 7.Department of Internal MedicineUniversity of FlorenceFlorenceItaly

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