A patient-specific therapeutic approach for tumour cell population extinction and drug toxicity reduction using control systems-based dose-profile design

Table 2 Bound limits of biological and therapeutic parameters applicable to human cases

Parameter	Lower limit	Upper limit	Reference
Circulating Lymphocyte, C (total population in the individual)	2.32 × 10⁹ cells (for not more than 6 months duration)	4.5 × 10¹¹ cells	Macintyre et al.[26] (upper limit); Jarosz et al.[27] (lower limit)
Natural Killer Cells, N (total population in the individual)	Negligible value (for not more than 3½ months duration)	5.85 × 10¹⁰ cells	Berrington et al.[28] (upper limit); Jawahar et al.[29] (lower limit)
Tumour-specific cytotoxic (CD8+) T-cells (CTL), L (total population of these cells in the individual)	Negligible value *	6.05 × 10¹⁰ cells	Dudley et al.[25] (upper limit); Roitt et al.[30] (lower limit)
Temozolomide infusion dosage rate, v_M	0	200 mg/m²/day (4.45mg/kg/day)	Perry [1]
Interleukin-2 infusion dosage rate, v_I	0	7.2 × 10⁴ I.U/kg/day	Perry [1]
Tumour Infiltrating lymphocyte (TIL) cumulative dosage (over full therapy duration, i.e., ∑ v_L)	0	13.7 × 10¹⁰ cells	Dudley et al.[25]

* This is applicable to the time after the tumour has been eliminated and pertains to population of the effective CD8+ T-cells specifically active against the particular tumour-lesion in the body; after tumour elimination, there is no possibility of stimulation by tumour cells to initiate the generation of the active tumour-specific CTL. The various bound values in the Table can be relaxed by 10-15%, this relaxation in the limits of physiological parameters being accommodated by the homeostatic adaptation of the physiological system [31]. Note: For clarifications of values of the bounds, see endnote ^a before the references bibliography.

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