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. 2013 Dec 26;10:68. doi: 10.1186/1742-4682-10-68

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Copyright © 2013 Kapoor et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Functional design of the therapeutic system using the Stimulus-Reconstruction approach.Output compartment (Tumour cell compartment): The state T (tumour cell population) is driven by state L (cytotoxic T-cell population in blood) and state M (chemotherapy drug temozolomide concentration in blood). Goal of system design is that the tumour cell population in this compartment decrease to a desired definitive value T_d (which is aimed to be zero); solving this compartment we arrive at L* and M* which are desired values respectively for cytotoxic T-cell population in blood and temozolomide concentration in blood required for complete tumour elimination. Intermediate compartment (Cytotoxic T-cell compartment): State L (cytotoxic T-cell population in blood) is driven by state I (interleukin-2 concentration in blood) and by state v_L (daily dosage of tumour-infiltrating leucocyte injection as immunotherapy). Solving this compartment, we get I* and v_L* which are the desired values respectively of interleukin-2 concentration in blood and dosage of tumour-infiltrating leucocyte required for tumour elimination. Input compartment-I (Interleukin-2 injection compartment): State I (Interleukin-2 concentration in blood) is driven by state v_I (daily dosage of interleukin-2 injection as immunotherapy). By solving this compartment, we arrive at v_I*, the desired value of interleukin-2 dosage required. Input compartment-II (Temozolomide injection compartment): State M (temozolomide concentration in blood) is driven by state v_M (daily dosage of temozolomide injection as chemotherapy). Solving this compartment, we arrive at v_M*, the desired value of temozolomide dosage required. Input compartment-III (Tumour-infiltrating leucocyte injection compartment): This furnishes daily dosage of tumour infiltrating leucocyte injection required, and is constructed from cytotoxic T-cell compartment above. Collateral compartment (normal tissue protection): This compartment comprises of circulating lymphocytes concentration in blood (C) and natural killer cell concentration in blood (N) which guard normal tissue against infection that may be caused by toxicity side-effect induced by the therapeutic agents.