Bcl-2 Peptide Fragments Targeting Anti-Apoptotic Resistance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer treatments face challenges due to drug resistance in cancer cells, particularly the overexpression of anti-apoptotic proteins like Bcl-2, which inhibits apoptosis and contributes to cancer progression and resistance to chemotherapy, limiting the effectiveness of immunotherapeutic strategies.
Innovation Solution
The use of MHC Class I restricted peptides derived from the Bcl-2 protein family, which are capable of binding to MHC Class I HLA molecules and eliciting CTL immune responses, providing a novel therapeutic and diagnostic approach by targeting Bcl-2 as a critical cellular factor for cancer treatment and diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapeutic agents are used to treat cancer, then cancer cells are targeted for destruction, but cancer cells develop resistance through mechanisms including drug inactivation, extrusion by cell membrane pumps, mutations of drug targets, and failure to initiate apoptosis
Solution Approach 1:
The patent converts the harmful anti-apoptotic function of Bcl-2 protein into a beneficial target for immune therapy. By identifying Bcl-2 as a tumor-associated antigen that can be recognized by T cells through MHC class I presentation, the invention transforms the protein's protective function for cancer cells into a vulnerability that can be exploited by the immune system to induce apoptosis and overcome drug resistance.
Solution Approach 2:
The patent uses MHC class I molecules as intermediaries to bridge the gap between the Bcl-2 protein and the T cell immune response. The Bcl-2 protein is processed and presented on MHC class I molecules, which then serve as the recognition target for cytotoxic T cells, enabling the immune system to indirectly target and destroy cancer cells expressing Bcl-2.
2Reliability
If Bcl-2 protein is overexpressed in cancer cells, then apoptosis is inhibited and drug resistance is conferred, but the protein can be targeted by immune system through MHC class I restricted peptides
Solution Approach 1:
The patent segments the Bcl-2 protein into smaller peptide fragments that can be presented by MHC class I molecules. This segmentation allows the immune system to recognize specific epitopes within the Bcl-2 protein, enabling T cell-mediated targeting while maintaining the overall structural integrity and functional relevance of the Bcl-2 protein as an anti-apoptotic factor.
3Reliability
If T-cell response is activated against tumor antigens, then tumor cells are recognized and destroyed, but the response is restricted to specific HLA molecules and peptides requiring precise matching
Solution Approach 1:
The patent identifies Bcl-2 as a universal tumor-associated antigen that is overexpressed in multiple types of cancers across different patients. By targeting this common protein through MHC class I restricted peptides, the invention creates a therapeutic approach that can be applied broadly across cancer types and patient populations, overcoming the limitation of HLA-restricted responses to specific antigens.
Data Source
AI summary
The present invention relates to proteins belonging to the Bcl-2 family and peptides fragments thereof for use in pharmaceutical compositions. The disclosed proteins and peptide fragments are in particularly useful in vaccine compositions for treatment of cancer. The invention furthermore relates to methods of treatment using said compositions. It is also an aspect of the invention to provide T-cells and T-cell receptors specifically recognising the disclosed proteins and peptide fragments.