CAR T Cell Modification for Solid Tumor Therapy
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Solution Overview
Problem
CAR T cell therapy for cancer, particularly in solid tumors, faces challenges such as physical barriers, tumor microenvironment immunosuppression, tumor heterogeneity, target specificity, and cell expansion in vivo, which limits its effectiveness.
Innovation Solution
Modified cells engineered to express specific molecules at enhanced or reduced levels, identified through single-cell profiling, are used to overcome these challenges by promoting antigen binding and signaling for persistent activation and expansion of CAR T cells without relying on cytokines, thereby enhancing their therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cells are used to treat solid tumors, then cancer treatment is achieved, but cell expansion in vivo is limited due to physical barriers and tumor microenvironment immunosuppression
Solution Approach 1:
The patent modifies molecular expression parameters in CAR T cells by overexpressing specific molecules (such as cytokines, co-stimulatory molecules, or transcription factors) identified through single-cell profiling analysis. This parameter change enables the cells to overcome physical barriers and immunosuppression in the tumor microenvironment, thereby improving both therapeutic effectiveness and cell expansion capability in vivo.
Solution Approach 2:
The patent performs preliminary genetic modification of CAR T cells ex vivo to enhance their functional properties before infusion. By pre-engineering the cells with optimized molecular expression profiles based on single-cell data, the therapy addresses the cell expansion limitation before the cells encounter the tumor microenvironment barriers, improving their ability to proliferate and persist in vivo.
2Adaptability or versatility
If conventional CAR T cell therapy is applied, then treatment is provided, but tumor heterogeneity and target specificity challenges reduce effectiveness
Solution Approach 1:
The patent applies local quality by identifying and modifying specific molecular expression patterns in CAR T cells that correspond to particular tumor subpopulations or microenvironmental conditions. Single-cell profiling reveals heterogeneous gene expression, and the therapy is tailored to enhance expression of molecules that confer specificity against diverse tumor targets, thereby improving adaptability without sacrificing effectiveness.
3Duration of action of moving object
If CAR T cells are engineered with standard molecular expression, then therapy is administered, but cell exhaustion and apoptosis limit sustained anti-tumor effects
Solution Approach 1:
The patent ensures continuity of useful action by engineering CAR T cells to continuously express protective and proliferative molecules identified through single-cell profiling. This continuous expression of key molecules (such as anti-apoptotic factors or metabolic enzymes) maintains cell functionality and prevents exhaustion over time, thereby extending the duration of anti-tumor effects and improving in vivo persistence.
Data Source
AI summary
The present disclosure describes compositions and methods for treating cancer. Embodiments relate to a cell modified to express one or more molecules at a level that is higher or lower than the level of the one or more molecules expressed by a cell that has not been modified to express the one or more molecules, wherein the one or more molecules comprise Cavin3, ZBED2, and MYC.