CAR-Expressing Immune Cells with Bcl-2 for Solid Tumor Efficacy
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Solution Overview
Problem
Current CAR-T cell therapies for solid tumors such as gastric cancer and pancreatic cancer have unsatisfactory efficacy, necessitating the development of novel CAR-T cell therapies that can specifically target and effectively eliminate tumor cells.
Innovation Solution
The development of immune effector cells that express chimeric antigen receptors (CARs) combined with the Bcl-2 protein or its functionally active fragments, which include antigen binding domains targeting CD20, CLDN18.2, or GPC-3, and are engineered to enhance in vitro and in vivo anti-tumor capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR-T cell therapy is used for solid tumors, then target recognition function is achieved, but anti-tumor efficacy is insufficient
Solution Approach 1:
The patent combines multiple functional elements into a single CAR structure: antigen binding domain (for target recognition), co-stimulatory domains (for T cell activation and persistence), and Bcl-2 protein (for apoptosis resistance). This merging of functions into one engineered receptor enables both specific targeting and enhanced anti-tumor efficacy that conventional CAR-T cells lack.
Solution Approach 2:
The CAR construct uses a composite structure combining different protein domains from various sources: antibody-derived antigen binding domain, CD28 or 4-1BB co-stimulatory domains, and Bcl-2 apoptotic resistance domain. This composite design creates a synergistic effect where each domain contributes a specific function, resulting in superior anti-tumor activity compared to single-domain constructs.
2Reliability
If CAR-T cells are engineered with multiple functions, then anti-tumor ability is enhanced, but cell complexity increases
Solution Approach 1:
Multiple functional domains are merged into a single polypeptide chain forming one integrated CAR protein. This consolidation avoids the complexity of expressing multiple separate proteins while achieving the same functional outcomes through a unified structure that is easier to engineer and control.
Solution Approach 2:
The CAR construct is designed as a universal platform that can target different antigens by simply changing the antigen binding domain, while maintaining the same co-stimulatory and survival domains. This multi-functionality reduces overall system complexity by using standardized modular components that can be reused across different therapeutic applications.
Data Source
AI summary
An immune effector cell, including and/or expressing a chimeric antigen receptor (CAR), and a Bcl-2 protein or a functionally active fragment thereof. A composition including the immune effector cell. A method for treating diseases and/or disorders, including administering to a subject in need thereof the immune effector cell, where the diseases and/or disorders include tumors.