Modulating Endothelial Proteins to Enhance T Cell Infiltration in Solid Tumors
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Solution Overview
Problem
Current cancer immunotherapy methods for solid tumors, such as adoptively transferred T cells and tumor vaccines, have shown limited success due to inadequate infiltration of effector cells into tumors, with the mechanisms governing T cell homing to tumors remaining poorly understood, particularly the role of the endothelium.
Innovation Solution
Modulating the expression or activity of proteins like Endothelin B receptor (ETRB), Endothelin-1 (ET-1), and Intercellular Adhesion Molecule 1 (ICAM-1) to enhance T cell homing to solid tumors, using compounds or compositions that reduce or increase their activity, thereby improving immunotherapy efficacy and prognosticating tumor behavior.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer immunotherapy using adoptively transferred T cells or tumor vaccines is applied, then immune response is activated, but T cell infiltration into tumors remains inadequate
Solution Approach 1:
The patent uses endothelial cells as intermediaries to facilitate T cell homing to tumors. By modulating endothelial cell proteins (ICAM-1, ETRB, ET-1), the invention creates a mediator system that bridges the gap between activated immune cells and tumor tissue, enabling effective T cell infiltration without directly manipulating T cells themselves.
Solution Approach 2:
The invention changes the expression levels of specific proteins (ICAM-1, ETRB, ET-1) in endothelial cells to optimize T cell homing. By upregulating or downregulating these molecular parameters, the patent creates favorable conditions for T cell infiltration into tumors, directly addressing the inadequate infiltration problem.
2Ease of operation
If T cell homing mechanisms are not understood, then immunotherapy can be administered, but treatment success is limited
Solution Approach 1:
The patent establishes a feedback mechanism by identifying specific endothelial cell proteins (ICAM-1, ETRB, ET-1) that regulate T cell homing. By monitoring and modulating these molecular markers, the invention provides feedback control over the T cell infiltration process, allowing optimization of immunotherapy outcomes based on measurable biological parameters.
3Device complexity
If endothelium role in T cell homing is not elucidated, then conventional treatment approaches are used, but tumor infiltration remains poor
Solution Approach 1:
The patent extracts and isolates the specific endothelial cell components (ICAM-1, ETRB, ET-1) that are critical for T cell homing. By separating these key molecular players from the complex endothelial system, the invention identifies the specific elements responsible for regulating T cell infiltration, enabling targeted modulation to improve tumor penetration.
Data Source
AI summary
The present invention provides methods of treating and enhancing efficacy of immunotherapy for a solid tumor in a subject, comprising the step of contacting the subject with a compound or composition that modulates the expression or activity of ETRB, ET-1, ICAM-1, or another protein found herein to play a role in homing of T cells to a solid tumor. The present invention also provides methods of prognosticating a solid tumor in a subject, comprising the step of measuring an expression level of a protein found herein to play a role in homing of T cells to a solid tumor, or a nucleotide molecule encoding same.