CAR Antigen Re-Expression Enhancer for Sustained CAR-T Killing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The therapeutic effect of CAR-T cell therapy diminishes over time due to the increasing proportion of tumor cells losing the CAR antigen on their surface, leading to reduced recognition and killing by CAR-T cells.
Innovation Solution
A therapeutic effect enhancer comprising lipid particles encapsulating CAR antigen and costimulatory factor nucleic acids is administered to reintroduce and express these antigens on tumor cells, enhancing their recognition and killing by CAR-T cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cell therapy is administered to treat tumors, then therapeutic effect is very high initially, but therapeutic effect gradually decreases over time due to antigen loss
Solution Approach 1:
The patent applies preliminary action by administering a nucleic acid composition encoding CAR antigen and costimulatory factor to the patient before CAR-T cell therapy. This preliminary treatment ensures that tumor cells express the target antigen and costimulatory factors in advance, so when CAR-T cells are administered, they can immediately recognize and kill the tumor cells effectively, preventing the initial therapeutic effect from being reduced due to antigen loss.
Solution Approach 2:
The patent implements continuity of useful action through repeated administrations of the nucleic acid composition at predetermined intervals during the course of CAR-T cell therapy. This continuous reinforcement ensures that tumor cells continuously express the CAR antigen and costimulatory factors, maintaining the therapeutic effect of CAR-T cells over an extended period and preventing antigen loss from reducing treatment efficacy.
2Adaptability or versatility
If tumor cells lose CAR antigen on surface, then CAR-T cell recognition and killing is avoided, but this leads to reduced therapeutic effect
Solution Approach 1:
The patent uses preliminary action by pre-treating tumor cells with nucleic acid composition that encodes CAR antigen and costimulatory factor before CAR-T cell administration. This ensures tumor cells express the necessary surface markers in advance, making them recognizable and killable by CAR-T cells, thus preventing the problem of antigen loss that would otherwise allow tumor cells to escape detection.
Solution Approach 2:
The patent implements feedback by monitoring the expression levels of CAR antigen and costimulatory factors on tumor cells, and adjusting the dosage and frequency of nucleic acid composition administrations accordingly. This feedback mechanism ensures that tumor cells maintain appropriate antigen expression levels, sustaining CAR-T cell recognition and killing capability throughout the treatment course.
Data Source
AI summary
According to one embodiment, a therapeutic effect enhancer for promoting a therapeutic effect of a CAR-T cell therapy is provided. The therapeutic effect enhancer includes a nucleic acid that contains a gene encoding a target antigen of a CAR, and a nucleic acid that contains a gene encoding a costimulatory factor.