US 2021/0343422 A1 · METHODS FOR DYNAMIC MODELING AND CLOSED-LOOP CONTROL OF INFLAMMATION

Abstract

The disclosure is directed to technologies for restoring proper regulation of the immune response and novel methods and systems for exogenously controlling immune cells in order to dynamically and predictively drive the immune response through pro-inflammatory activity to anti-inflammatory activity, mimicking the immune system's natural progression through these states. Embodiments of the present disclosure relate generally to methods and systems for dynamic predictive modeling and control of inflammation and the immune response, and more specifically to methods and systems for predictive modeling and control of the inflammatory state of immune cells via temporally regulated immune-modulating stimuli.

Claims36

Dependent claims

A method comprising:

delivering a first stimulus that elicits a change in the inflammatory state of an immune cell;
and
detecting the change in the inflammatory state of the immune cell;
wherein a second stimulus is based on the change in the inflammatory state of the immune cell in order to model and/or control the inflammatory response of the immune cell;
and
wherein the change in the inflammatory state of the immune cell to the first stimulus and, if delivered, the second stimulus, is predicted by:
fitting an engineering model to input/output data obtained by stimulating cells;
and
selecting the best fitting engineering model based on the input/output data and applying that model to future input/output data.

6 more elements

A system comprising:

a fluid chamber comprising at least a first inlet, at least a first outlet, and an immune cell;
a controller in fluid communication with the fluid chamber configured to:
deliver a first stimulus through the first inlet, wherein the stimulus elicits a change in the inflammatory state of the immune cell;
and
deliver a second stimulus;
wherein the first stimulus causes the immune cell to change from a quiescent state to a pro-inflammatory state, and/or the pro-inflammatory state to an anti-inflammatory state;
and
a detector in fluid communication with the fluid chamber configured to:
detect the change in the inflammatory state of the immune cell;
and
generate input/output data indicative of the change in the inflammatory state of the immune cell;
wherein the change in the inflammatory state of the immune cell is detected by measuring a marker characteristic of the inflammatory state;
wherein a marker characteristic of the pro-inflammatory state comprises one or more of iNOS, SOCS3, TLR4, TLR2, IL-1R, MHCII, CD68, CD80, CD86, TLR2, TNFα, IL1α, ITAM1, IL113, HIF1α, IL-12b, KCna3, GFAP, CLEC7a, Vimentin, CD69, CD27, CD45, CD44, and CCR7;
and
wherein a marker characteristic of the anti-inflammatory state or homeostatic state comprises one or more of CD163, MHCII, SR, CD206, CD200R, TGM2, DecoyR, IL-1R, Ym1/2, Fizz1, Arg1, CD86, TLR1, TLR8, VEGF, Arg1, APOE, TIMP2, IGF1, DPP6, P2Rγ12, TMEM119, BIN1, PTGS1, and CD62;
wherein the second stimulus is based on the change in the inflammatory state of the immune cell in order to model and/or control the inflammatory response of the immune cell;
and
wherein the change in the inflammatory state of the immune cell to each of the first stimulus and second stimulus is predicted by:
fitting an engineering model to the input/output data obtained by stimulating cells within the chamber;
and
selecting the best fitting engineering model based on the input/output data and applying that model to future input/output data.

18 more elements

Dependencies are inferred from the claim text.

Methods for dynamic modeling and closed-loop control of inflammation

Life of this patent

Methods for dynamic modeling and closed-loop control of inflammation

Life of this patent

Abstract

Claims36