CAR-T Cells Expressing PD-L1 Blockers for Solid Tumor Survival
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Solution Overview
Problem
Current chimeric antigen receptor (CAR) T lymphocytes have limited efficacy and survival in solid tumors due to the inhibitory effects of PD-L1 expressed by tumor cells, which bind to PD-1 on immune effector cells, leading to immune incompetence and reduced anti-tumor activity.
Innovation Solution
Modifying immune effector cells to express a PD-L1 blocking agent, such as soluble PD-1 (sPD-1), a fusion peptide of sPD-1 and CH3 domain of hIgG4e1-Fc, or a specific anti-PD-L1 antibody, combined with a chimeric antigen receptor that includes an extracellular antigen-binding region, a transmembrane region, and an intracellular signaling region, to block the interaction between PD-L1 and PD-1, thereby enhancing their survival and function in tumor tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune effector cells are modified with chimeric antigen receptors to enhance anti-tumor activity, then tumor targeting capability is improved, but survival and activity in solid tumors remain poor due to PD-L1 inhibition
Solution Approach 1:
The patent introduces a PD-L1 blocking agent as an intermediary substance that prevents the interaction between PD-L1 on tumor cells and PD-1 on immune effector cells. This mediator blocks the inhibitory signal transmission, thereby maintaining the anti-tumor activity of immune effector cells in the tumor microenvironment without requiring modification of the effector cells themselves with complex CAR structures.
2Duration of action of moving object
If PD-L1 blocking agents are introduced to prevent immune inhibition, then survival and activity of immune effector cells are enhanced, but the complexity of the treatment system increases
Solution Approach 1:
The patent enables immune effector cells to self-produce the PD-L1 blocking agent through genetic modification. The cells contain an expression system that autonomously synthesizes the blocking agent within the tumor microenvironment, eliminating the need for external administration of separate blocking agents and simplifying the overall treatment system while maintaining enhanced survival and activity.
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
The expression of PD-L1 blocking agents on CAR-modified immune effector cells increases their survival and anti-tumor activity by preventing immune inhibition, allowing for more effective targeting and killing of tumor cells, even in solid tumors where PD-L1 is highly expressed.
Implementation Method 1
a PD-L1 (programmed death ligand 1) blocking agent (Blocker)... soluble PD-1 (sPD-1)... a specific anti-PD-L1 antibody
Data Source
AI summary
Provided is a chimeric antigen receptor-modified immune effector cell carrying a procedural death ligand 1 (PD-L1) blocking agent. Also provided is a method for secreting and expressing a PD-L1 blocking agent using the immune effector cell as a carrier to improve the anti-tumour effect of the chimeric antigen receptor-modified immune effector cell.