SDF-1 Gradient Modulation for Leukocyte Infiltration
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Solution Overview
Problem
Current cancer therapies, particularly immunotherapy, face challenges in effectively accessing tumors due to the chemokine SDF-1 signaling pathway, which attracts immune suppressive cells and limits the infiltration of cytotoxic leukocytes, hindering the immune response against tumors.
Innovation Solution
Development of molecules that inhibit the signaling between SDF-1 and its receptors CXCR4 and CXCR7 to modulate the distribution of tumor-infiltrating leukocytes, establish an SDF-1 gradient, and induce a leukocyte-mediated immune response, enhancing the infiltration and activity of immune cells like NK cells and T cells within tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If SDF-1 signaling pathway is utilized to recruit immune cells to tumors, then immune cell infiltration is enhanced, but immune suppressive cells are also attracted which limits the efficacy of cytotoxic leukocytes
Solution Approach 1:
The patent applies local quality by creating a spatially differentiated SDF-1 gradient where the chemokine concentration varies across different regions of the tumor microenvironment. This gradient enables selective recruitment of immune cells to specific zones, allowing cytotoxic leukocytes to infiltrate tumor regions while limiting the accumulation of immune suppressive cells in other areas, thus resolving the contradiction between enhancing immune cell infiltration and avoiding immune suppressive cell attraction
Solution Approach 2:
The patent utilizes parameter changes by modulating the concentration and distribution of SDF-1 throughout the tumor microenvironment. By controlling the spatial and temporal parameters of SDF-1 signaling, the invention optimizes the recruitment of cytotoxic immune cells while minimizing the attraction of immune suppressive cells, thereby overcoming the limitation where enhanced infiltration coincides with harmful cell recruitment
2Speed
If SDF-1 gradient is established to guide leukocyte migration, then cytotoxic leukocyte infiltration is promoted, but the existing signaling axis supports immune suppressive cell recruitment
Solution Approach 1:
The patent introduces an intermediary approach by using SDF-1 as a mediator to guide leukocyte migration through controlled gradient formation. This intermediary signaling mechanism enables cytotoxic leukocytes to migrate efficiently toward tumor regions while the gradient structure itself acts as a directional guide that can be optimized to exclude or limit immune suppressive cells, thus maintaining both high migration speed and reliable immune response efficacy
Solution Approach 2:
The patent applies dynamics by creating a dynamic SDF-1 gradient that can adapt and evolve within the tumor microenvironment. This dynamic gradient allows the system to optimize leukocyte migration patterns over time, enhancing the speed and efficiency of cytotoxic leukocyte infiltration while simultaneously adjusting to prevent or reduce the recruitment of immune suppressive cells, thereby maintaining reliable immune response efficacy
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 approach increases the infiltration of cytotoxic immune cells into tumors, promotes a pro-inflammatory immune environment, and enhances tumor cell killing, potentially improving treatment outcomes for various cancer types by disrupting the SDF-1/CXCR4 and SDF-1/CXCR7 axes.
Implementation Method 1
molecules capable of inhibiting signaling between SDF-1 and CXCR4 and/or CXCR7
Implementation Method 2
establish an SDF-1 gradient, induce leukocyte mediated immune response against the tumor
Data Source
AI summary
The present invention is related to a molecule capable of inhibiting signaling between SDF-1 and CXCR4 and/or CXCR7, wherein the molecule is for use in a method of modulating the number and/or the spatial distribution of tumor-infiltrating leukocytes in a tumor and/or metastases.