An Adaptive Control Scheme for Interleukin-2 Therapy

Khailaie, Sahamoddin; Montaseri, Ghazal; Meyer‐Hermann, Michael

doi:10.1016/j.isci.2020.101663

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Based on the analysis, we developed an ordinary differential equations (ODEs) model to investigate the dynamic processes of the immune response during IL-2 treatment in our model ( Khailaie et al., 2020 ; Sontag, 2017 ).

and

denote the density of APC, TN, Treg d , Treg f , and NK cell, respectively, they all are in the unit mm −3 .…”

Section: Resultsmentioning

confidence: 99%

Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus

Gao

Sun

et al. 2022

iScience

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and

denote the density of APC, TN, Treg d , Treg f , and NK cell, respectively, they all are in the unit mm −3 .…”

Section: Resultsmentioning

confidence: 99%

Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus

Gao

Sun

et al. 2022

iScience

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“…The application of this design approach is particularly pertinent to IL-2 given current intense interest in engineering IL-2 as a cancer immunotherapeutic. Simultaneous activation of Teffs and Tregs is a common feature of IL-2 therapy ( 33 ). However, Tregs suppress the activity of Teffs and limit immune activation ( 19 ), suggesting a need for IL-2R “β/γ” biased IL-2 analogs which we have designed here.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-2 superkines by computational design

Ren

Chu

Jude

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance While computational engineering of therapeutic proteins is a desirable goal, in practice the optimization of protein–protein interactions requires substantial experimental intervention. We present here a computational approach that focuses on stabilizing core protein structures rather than engineering the protein–protein interface. Using this approach, we designed thermostabilized interleukin-2 (IL-2) variants that bind tightly to their receptor without experimental optimization, mimicking the properties of the yeast-display engineered IL-2 variant “super-2.” Our results suggest that structure-guided stabilization may be a general method for in silico affinity maturation of protein–protein interactions.

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“…Human Tregs are cultured in high amounts of IL-2 and NSG mice do not have an endogenous source of IL-2. This dependence on IL-2 may result in a loss of human Tregs in vivo, and IL-2 has been given to clinical patients injected with in vitro expanded Tregs (18,22,35). To test whether additional IL2 treatment would promote the persistence of Tregs in these mSOD1-NSG mice, mice were given injections of IL-2 i.p.…”

Section: Pro-inflammatory Cytokines Are Found In the Spinal Cords Of Msod1-nsg Mice And Increase As Disease Progressesmentioning

confidence: 99%

mSOD1-NSG mice: a new in vivo model to test human T cells in ALS

Graber¹,

Sentman²,

Cook³

et al. 2021

Preprint

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unclear etiology and few treatment options. Engineering of human cells for therapy has great potential to provide a means to create long-lived therapeutics that can respond to local signals within tissues. One challenge for development of human cell therapeutics is to have disease models that do not reject transplanted human cells. G93A mutant superoxide dismutase-1 (mSOD1) transgenic mouse model is a robust disease model for ALS, with development of local inflammation, activation of microglia and astrocytes, motor neuron death, and development of paralysis. To create a mouse model for ALS that permits the transplantation of human T cells without immune-mediate rejection, we bred the G93A transgene onto the NOD-SCID-IL-2Rγ-deficient (NSG) mouse model to create mSOD1-NSG mice. We report that mSOD1-NSG mice develop a progressive ALS-like disease with microgliosis, astrogliosis, and paralysis development with an average onset at 11 weeks and end-stage at 14 weeks. Transplanted human T regulatory cells survive in these mice for at least 60 days. This mSOD1-NSG mouse model for ALS can be used to test human T cell-based therapeutics, and it may be helpful to test any human cell-based therapy for ALS.

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An Adaptive Control Scheme for Interleukin-2 Therapy

Cited by 5 publications

References 40 publications

Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus

Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus

Interleukin-2 superkines by computational design

mSOD1-NSG mice: a new in vivo model to test human T cells in ALS

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