An Adaptive Control Scheme for Interleukin-2 Therapy

Sahamoddin Khailaie; Ghazal Montaseri; Michael Meyer-Hermann

doi:10.1016/j.isci.2020.101663

An Adaptive Control Scheme for Interleukin-2 Therapy

iScience. 2020 Oct 12;23(11):101663. doi: 10.1016/j.isci.2020.101663. eCollection 2020 Nov 20.

Authors

Sahamoddin Khailaie^{1

2}, Ghazal Montaseri^{1

3}, Michael Meyer-Hermann^{1

2

4}

Affiliations

¹ Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
² Centre for Individualised Infection Medicine (CIIM), Hannover, Germany.
³ Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.
⁴ Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.

Abstract

Regulatory T cells (Treg) are suppressor cells that control self-reactive and excessive effector conventional T helper cell (Tconv) responses. Breakdown of the balance between Tregs and Tconvs is a hallmark of autoimmune and inflammatory diseases. Interleukin-2 (IL-2) is a growth factor for both populations and subtle leverage to restore the healthy immune balance in IL-2 therapy. By using a mechanistic mathematical model, we introduced an adaptive control strategy to design the minimal therapeutic IL-2 dosage required to increase and stabilize Treg population and restrict inflammatory response. This adaptive protocol allows for dose adjustments based on the feedback of the immune kinetics of the patient. Our simulation results showed that a minimal Treg population was required to restrict the transient side effect of IL-2 injections on the effector Tconv response. In silico results suggested that a combination of IL-2 and adoptive Treg transfer therapies can limit this side effect.

Keywords: Biological Sciences; Immunology; Mathematical Bioscience.