Phospho-peptide Identification via MHC Class I Mediators
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Solution Overview
Problem
Current immunotherapy methods for cancer, particularly melanoma, face challenges in identifying effective tumor antigens and developing targeted treatments due to the unpredictability of phosphorylated peptides presented on cancer cells.
Innovation Solution
The development of novel tumor-specific phosphorylated peptides and antibodies that bind to MHC molecules, specifically identified through mass spectrometry for HLA-A*0201 and HLA-B7, which can be used as diagnostic indicators and therapeutic agents to target cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy methods are used to identify tumor antigens, then treatment approaches can be developed, but the unpredictability of phosphorylated peptides makes identification difficult and reduces reliability
Solution Approach 1:
The patent uses MHC molecules as intermediaries to capture and present phosphorylated peptides from cancer cells. By employing MHC class I and class II molecules as mediators, the method transforms the difficult task of directly identifying unpredictable phosphorylated peptides into a more reliable process of capturing peptides that are naturally presented by MHC molecules on the surface of cancer cells, thereby resolving the contradiction between reliability and detection difficulty
Solution Approach 2:
The patent replaces conventional mechanical or chemical extraction methods for identifying tumor antigens with a biological recognition system. Instead of using mechanical separation or chemical analysis to identify phosphorylated peptides, the method uses the natural immune system's MHC molecules to selectively bind and present antigenic peptides, substituting a biological recognition mechanism for traditional detection approaches and improving both reliability and ease of identification
2Reliability
If MHC molecules are used to capture phosphorylated peptides, then identification reliability improves, but the complexity of the system increases due to multiple MHC alleles and peptide variability
Solution Approach 1:
The patent employs both MHC class I and MHC class II molecules in the diagnostic system, creating a multi-functional approach that can capture different types of antigenic peptides through different MHC pathways. This universal system handles the complexity of multiple MHC alleles by utilizing the natural diversity of MHC molecules to present a broader range of potential tumor antigens, thereby maintaining high reliability while managing system complexity through functional redundancy
Solution Approach 2:
The patent segments the complex MHC system into distinct class I and class II pathways, each handling specific types of antigen presentation. By dividing the overall antigen identification process into separate MHC class I and class II components, the method manages the inherent complexity of the MHC system while maintaining comprehensive coverage of potential tumor antigens, resolving the contradiction between reliability and system complexity
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
These peptides stimulate an immune response and can be used to recognize and target cancer cells, potentially improving treatment outcomes for melanoma and other cancers by enhancing the body's immune response against tumor-specific CTLs.
Implementation Method 1
utilizing mass spectrometry to identify the peptides
Implementation Method 2
interaction of the T cell receptor, located on the surface of the CTL, with what is generically referred to as an MHC-peptide complex which is located on the surface of the cancerous cell
Implementation Method 3
Cytotoxic T lymphocytes (CTL) are specialized T cells that primarily function by recognizing and killing cancerous cells
Data Source
AI summary
The present invention describes novel tumor-specific phosphorylated peptides, nucleic acids encoding those peptides, and antibodies generated against said peptides. The genes, peptides, and antibodies described herein may be used as diagnostic indicators of the presence of breast cancer and/or used in therapeutics to treat breast cancer.