Globally Activated Monocytes for Selective Dendritic Cell Production
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Solution Overview
Problem
Existing methods for producing dendritic cells, such as extracorporeal photopheresis (ECP), result in complex mixtures of immuno-stimulatory and immuno-suppressive cells, limiting their therapeutic efficacy, and lack the ability to selectively produce these cells outside the body.
Innovation Solution
A method involving physical activation of monocytes using mechanical stress and interaction with plasma components, without photoactivatable agents or UV-A, to produce globally activated monocytes that can differentiate into either immuno-stimulatory or immuno-suppressive dendritic cells, characterized by specific molecular markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If ECP or ECP-like processes are used to produce dendritic cells, then dendritic cells are generated without requiring exogenous cytokine stimulation, but the result is a complex mixture of immuno-stimulatory and immuno-suppressive DC that limits therapeutic efficacy
Solution Approach 1:
The patent segments the dendritic cell production process into distinct pathways: one for immuno-stimulatory DC (using physical forces like mechanical stress and UV irradiation without 8-MOP) and another for immuno-suppressive DC (using 8-MOP and UV-A). This segmentation allows selective production of desired DC types rather than obtaining a complex mixture, thereby resolving the contradiction between ease of manufacture and manufacturing precision.
Solution Approach 2:
The patent applies local quality by using different treatment conditions for different desired outcomes: physical forces and UV irradiation without 8-MOP for immuno-stimulatory DC, and 8-MOP with UV-A for immuno-suppressive DC. This localized application of different quality parameters enables precise control over DC differentiation, resolving the contradiction between ease of manufacture and manufacturing precision.
2Adaptability or versatility
If 8-MOP and UV-A are applied to differentiate monocytes into dendritic cells, then immuno-suppressive or tolerogenic DC are produced, but this limits the ability to produce immuno-stimulatory DC
Solution Approach 1:
The patent introduces dynamics by making the differentiation pathway adjustable: the same monocyte population can be directed toward immuno-stimulatory or immuno-suppressive DC depending on the applied treatment conditions. This dynamic control allows the system to adapt to different therapeutic needs while maintaining precision through defined treatment parameters.
Solution Approach 2:
The patent uses parameter changes to control DC differentiation: changing the presence or absence of 8-MOP, the type of irradiation (UV vs UV-A), and the application of physical forces allows selective production of either immuno-stimulatory or immuno-suppressive DC. This parameter-based control resolves the contradiction between adaptability and manufacturing precision.
3Manufacturing precision
If physical forces such as mechanical stress are applied to activate monocytes, then globally activated monocytes are produced that can differentiate into either immuno-stimulatory or immuno-suppressive DC, but the process requires precise control of multiple parameters
Solution Approach 1:
The patent applies universality by using a single activation approach (physical forces) that can lead to multiple differentiation outcomes depending on subsequent treatment conditions. This multi-functional activation method allows the same initial step to serve different therapeutic purposes, reducing device complexity while maintaining manufacturing precision.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method allows for the production of monocytes with enhanced phagocytic activity, usable for tumor killing, wound healing, and regenerative medicine, and can differentiate into dendritic cells with desired immunological properties, enhancing therapeutic outcomes.
Implementation Method 1
subjecting an extracorporeal quantity of a mammalian subject's blood sample, which comprises monocytes, to a physical force such that the monocytes are globally activated
Implementation Method 2
passing or cycling said extracorporeal quantity of said mammalian subject's blood sample through a flow chamber of a device, which allows adjustment of the flow rate such that a shear force is applied to the monocytes
Data Source
AI summary
The present invention relates to methods for producing immuno-stimulatory autologous dendritic cells. The present invention further relates to the use of such cells for treating patients suffering from hyper-proliferative disease such as cancer.