Dual CAR T Cells for Solid Tumor Persistence
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Solution Overview
Problem
Current CAR therapies for treating tumors face challenges with limited persistence and proliferation of CAR-expressing cells in vivo, leading to variable efficacy in treating cancers beyond B-cell malignancies.
Innovation Solution
Engineering immune effector cells, such as T cells, to express a first chimeric antigen receptor (CAR) targeting B-Cell antigens and a second CAR targeting tumor antigens other than B-Cell antigens, enhancing the persistence and proliferation of CAR-expressing cells by binding to specific antigens like BCMA, CD19, EGFRvIII, and mesothelin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR therapy is used to treat tumors, then targeted immune response is achieved, but persistence and proliferation of CAR-expressing cells is limited
Solution Approach 1:
The patent combines two different CARs in a single immune effector cell: one targeting B-cell antigens (e.g., CD19, BCMA) and another targeting solid tumor antigens (e.g., EGFRvIII, mesothelin). This dual CAR configuration allows the cell to persist longer by engaging multiple antigen targets, thereby resolving the contradiction between achieving reliable anti-tumor efficacy and maintaining prolonged persistence of CAR-expressing cells.
Solution Approach 2:
The engineered immune effector cell is designed with multi-functionality by expressing CARs that recognize different antigen types across various tumor categories. This universal targeting capability enables the same cell population to effectively hunt and kill diverse tumor cells, extending their functional lifespan and persistence in the patient's body while maintaining high anti-tumor efficacy.
2Reliability
If CAR therapy is used to treat tumors, then targeted immune response is achieved, but proliferation of CAR-expressing cells is limited
Solution Approach 1:
By merging B-cell targeting CARs with solid tumor targeting CARs within the same immune effector cell, the patent creates a dual-functional system that enhances proliferation signals. The combination of different antigen-specific CARs provides multiple activation pathways, leading to increased cell proliferation and improved productivity while maintaining targeted anti-tumor response.
3Adaptability or versatility
If single CAR targeting B-cell antigens is used, then B-cell malignancies are treated effectively, but other cancers cannot be treated
Solution Approach 1:
The patent implements universality by designing immune effector cells that express multiple CARs with different specificities - some targeting B-cell antigens and others targeting solid tumor antigens. This multi-functional design enables the same cell population to effectively treat both B-cell malignancies and solid tumors, dramatically expanding treatment scope while maintaining high anti-tumor efficacy for each cancer type.
Data Source
AI summary
The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein by administration of a cell comprising a chimeric antigen receptor that binds a B-Cell antigen and a chimeric antigen receptor which binds a tumor antigen.