A mathematical model of combined bacillus Calmette-Guerin (BCG) and interleukin (IL)-2 immunotherapy of superficial bladder cancer

J Theor Biol. 2011 May 21;277(1):27-40. doi: 10.1016/j.jtbi.2011.02.008. Epub 2011 Feb 18.


We report a mathematical model that describes the growth of superficial bladder cancer and the effect thereupon of immunotherapy based on the administration of Bacillus Calmette-Guerin (BCG) combined or not with interleukin-2 (IL-2). Intravesical instillations of BCG performed after surgical removal of tumors represents an established treatment with approximately 50% success rate. So far, attempts to improve this efficiency have not led to essential changes. However, convincing clinical results have been reported on the combination of IL-2 to BCG, even though this is still not applied in current practice. The present model provides insights into the dynamical outcomes arising in the bladder from the interactions of immune cells with tumor cells in the course of BCG therapy associated or not with IL-2. Specifically, from the simulations performed using seven ordinary and non-linear differential equations we obtained indications on the conditions that would result in successful bladder cancer treatment. We show that immune cells -effector lymphocytes and antigen-presenting cells-expand and reach a sustainable plateau under BCG treatment, which may account for its beneficial effect, resulting from inflammatory "side-effects" which eliminate residual or eventual newly arising tumor cells, providing thus protection from further cancer development. We find, however, that IL-2 does not actually potentiate the effect of BCG as regards tumor cell eradication. Hence, associating both under the conditions simulated should not result in more efficient treatment of bladder cancer patients.

MeSH terms

  • BCG Vaccine / administration & dosage
  • BCG Vaccine / pharmacology
  • BCG Vaccine / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Computer Simulation
  • Disease Progression
  • Humans
  • Immunotherapy*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Models, Biological*
  • Time Factors
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / pathology


  • BCG Vaccine
  • Interleukin-2