TCR-Modified NK Cells Target EGFR Lung Cancer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cell therapies, including those targeting solid tumors, face limitations in effectively targeting and killing cancer cells due to low specificity and efficacy, particularly in treating EGFR-mutant lung cancers where immune checkpoint inhibitors are ineffective after initial response.
Innovation Solution
Development of a T cell receptor (TCR) specific to the MHC-1-L858R neoantigen complex, combined with an Fc receptor, is introduced into NK cells to enhance their targeting and killing capabilities, utilizing a platform that predicts tumor-specific antigens with high accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If NK cells are used for cell therapy, then they can target and kill malignant cells through non-specific recognition, but they lack specificity for tumor antigens and cannot effectively target solid tumors
Solution Approach 1:
The patent combines NK cells with T cell receptors (TCR) that specifically recognize tumor antigens. The TCR is genetically modified into the NK cells, creating a hybrid cell that possesses both the non-specific killing capability of NK cells and the antigen-specific recognition of T cells, thereby resolving the contradiction between versatility and precision in tumor targeting
Solution Approach 2:
The modified NK cells acquire multi-functionality by expressing TCR alongside their natural NK cell receptors. This allows them to perform both non-specific cytotoxicity (innate immune function) and antigen-specific recognition (adaptive immune function), enabling them to effectively target solid tumors while maintaining broad anti-tumor activity
2Productivity
If conventional cell therapies are used, then they can proliferate and utilize immune cells targeting tumors, but they are ineffective after immune checkpoint inhibitors lose efficacy due to acquired tolerance
Solution Approach 1:
The patent changes the functional parameters of the immune cells by genetically modifying NK cells to express specific TCRs. This creates a new cell product with altered recognition capabilities that can target tumor antigens independently of the immune checkpoint pathways that have become tolerant, thereby maintaining therapy efficacy when conventional approaches fail
3Measurement precision
If TCR is introduced into NK cells, then tumor antigen specificity is improved, but the complexity of cell therapy development increases
Solution Approach 1:
The patent uses viral vectors as intermediaries to deliver and integrate the TCR genes into NK cells. This intermediary approach simplifies the complex process of genetic modification by providing an efficient, standardized method for introducing and expressing the desired TCR sequences, thereby reducing overall development complexity while achieving high antigen specificity
Data Source
AI summary
The present specification provides not only an antigen-specific T cell receptor but also a nucleic acid, a vector, and an immune cell comprising the T cell receptor, and a method using same.