TY - JOUR
T1 - A mathematical model of combined bacillus Calmette-Guerin (BCG) and interleukin (IL)-2 immunotherapy of superficial bladder cancer
AU - Bunimovich-Mendrazitsky, Svetlana
AU - Claude Gluckman, Jean
AU - Chaskalovic, Joel
N1 - Funding Information:
Svetlana Bunimovich-Mendrazitsky thanks Professors Lewi Stone and Helen Byrne for fruitful and stimulating discussions. The primary model has been developed while visiting Nottingham University (UK) and working with Professor Helen Byrne. We are grateful to Professor Leonid Hanin for fruitful and stimulating discussions. Part of this study was supported by a fellowship from the Edmond J. Safra Bioinformatics program at Tel-Aviv University. We gratefully acknowledge the financial assistance received from the British Council through the Research Exchange Programme with Nottingham University.
PY - 2011/5/21
Y1 - 2011/5/21
N2 - 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.
AB - 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.
KW - BCG and IL-2 combined therapy
KW - BCG immunotherapy
KW - Bladder cancer
KW - Immune system cells dynamics
UR - http://www.scopus.com/inward/record.url?scp=79952326929&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2011.02.008
DO - 10.1016/j.jtbi.2011.02.008
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C2 - 21334346
AN - SCOPUS:79952326929
SN - 0022-5193
VL - 277
SP - 27
EP - 40
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
IS - 1
ER -