Mutant RAS TCR Engineering for Targeted Cancer Recognition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies for treating cancers with oncogenic RAS mutations, such as KRAS, NRAS, and HRAS, are ineffective and often result in high toxicity and immunogenicity, necessitating the development of novel T cell receptors (TCRs) that can target mutated RAS peptides with minimal side effects.
Innovation Solution
Development of TCRs that specifically target RAS peptides with mutations like G12D, G12V, or G12C, which are recombinantly expressed and can be integrated into T cells to enhance their ability to recognize and attack cancer cells associated with these mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat cancers with RAS mutations, then treatment coverage is provided, but effectiveness is poor and toxicity is high
Solution Approach 1:
The patent changes the therapeutic approach from conventional chemotherapy to T cell receptor-based immunotherapy, fundamentally altering the treatment mechanism to achieve better effectiveness with reduced toxicity. The TCRs are engineered with specific binding characteristics to recognize mutated RAS peptides while sparing healthy cells.
Solution Approach 2:
The patent introduces T cell receptors as intermediary molecules that mediate the immune system's recognition and attack on cancer cells expressing mutated RAS proteins. These TCRs serve as the bridge between the immune system and the tumor cells, enabling targeted therapy.
2Power
If TCRs are developed to target mutated RAS peptides, then cancer eradication potency is enhanced, but immunogenicity may increase
Solution Approach 1:
The patent applies local quality by designing TCRs with specific binding properties that recognize only mutated RAS peptides (such as G12D, G12V, G12C mutations) while maintaining low immunogenicity. The TCRs are engineered to have high affinity for the specific mutant epitopes presented by HLA molecules, enabling potent targeted action without widespread immune activation.
3Manufacturing precision
If TCRs are designed for high specificity to mutated RAS, then targeting precision is improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the complex task of creating targeted therapy into distinct components: identifying specific RAS mutations (G12D, G12V, G12C), designing TCRs with specific binding characteristics, and engineering T cells to express these TCRs. This segmentation allows for systematic development and optimization of each component.
Solution Approach 2:
The patent develops universal TCR platforms that can target multiple RAS mutation types. The TCR design approach creates a framework that can be adapted to different RAS mutants, reducing overall development complexity while maintaining high targeting precision across multiple cancer types.
Data Source
AI summary
The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.