T Cell Receptor for WT1 Peptide Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer treatments, such as cancer vaccinations, face limitations due to the reliance on patient immunity, which is compromised by chemotherapy and radiation therapy, leading to reduced effectiveness, and there is a lack of direct methods to detect cancer antigens like WT1 peptides presented by HLA-A*24:02 on cancer cells.
Innovation Solution
Development of a T cell receptor (TCR) capable of recognizing both wildtype and mutant WT1 peptides presented by HLA-A*24:02, allowing for the efficient detection and targeting of cancer cells, along with DNA encoding the TCR and transformed cells expressing these receptors for therapeutic and diagnostic purposes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer vaccination is performed using conventional methods, then the treatment activates patient immunity to eliminate cancer, but the effectiveness is reduced when patient immunity is compromised by chemotherapy and radiation therapy
Solution Approach 1:
The patent uses a T cell receptor (TCR) as an intermediary tool to detect and target cancer cells. The TCR specifically recognizes HLA-A*24:02 presented WT1 peptides on cancer cells, serving as a mediator between the treatment system and the cancer target, enabling effective action even when overall patient immunity is compromised
Solution Approach 2:
The patent identifies and targets a specific parameter (HLA-A*24:02 restriction) to achieve effective cancer cell recognition. By focusing on this specific HLA restriction and using TCR technology, the system achieves high specificity and reliability in cancer targeting, overcoming the general problem of compromised immunity
2Productivity
If conventional cancer treatments (surgery, anticancer drug, radiation therapy) are used, then cancer is treated, but there is no improvement observed and patients become 'cancer refugees' searching for further treatments
Solution Approach 1:
The patent replaces conventional mechanical and chemical treatment methods with an immunological mechanism-based approach. Using TCR technology to specifically recognize and target cancer cells through the immune system provides a new mechanism of action that differs from traditional surgery, chemotherapy, and radiation, potentially achieving better treatment responses
3Measurement precision
If there is a lack of direct detection methods for cancer antigens, then cancer diagnosis accuracy is reduced, but developing such methods requires new technological approaches
Solution Approach 1:
The patent uses T cell receptors as biological copies or proxies to detect cancer antigens. Instead of directly detecting the cancer antigen itself, the TCR serves as a copy that binds to the HLA-A*24:02 presented peptide, providing an indirect but highly specific detection method that achieves high measurement precision
Solution Approach 2:
The patent changes the detection parameter from direct antigen detection to HLA-restricted peptide detection. By using TCRs that specifically recognize HLA-A*24:02 presented WT1 peptides, the system achieves high detection accuracy through a different parameter (HLA restriction specificity) that provides both sensitivity and specificity
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
Enables the specific recognition and targeting of cancer cells expressing WT1 peptides, improving cancer treatment efficacy and providing a means for direct detection of WT1 peptides, enhancing the accuracy of cancer diagnoses and treatments.
Implementation Method 1
T cell receptor (TCR) capable of recognizing both wildtype and mutant WT1 peptides presented by HLA-A*24:02
Data Source
AI summary
A method has been developed to efficiently proliferate and culture a CTL specific to WT1 peptides under limiting dilution conditions. Utilizing this method, CTLs capable of recognizing both a state where a wildtype WT1 specific peptide is presented by HLA-A*24:02 and a state where a mutant WT1 specific peptide is presented by HLA-A*24:02 have been successfully obtained.