Brachyury Deletion Mutant Polypeptides for Cancer Immunotherapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapeutic interventions for cancer lack effective targets that induce a specific immune response against tumor cells, particularly molecules essential for malignant transformation and tumor progression, such as Brachyury, which are overexpressed in various carcinomas but have not been adequately addressed for inducing a robust CD4 and CD8 T cell response.
Innovation Solution
Development of Brachyury deletion mutant polypeptides and nucleic acids that reduce DNA binding activity, administered via non-yeast vectors and cells to induce a specific immune response, including CD4+ T cell responses, for treating or preventing cancer by inhibiting cancer cell growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Brachyury deletion mutant polypeptides are administered to induce immune response, then CD4+ and CD8+ T cell response is enhanced, but DNA binding activity of Brachyury is reduced
Solution Approach 1:
The patent extracts and removes the DNA binding domain (amino acid residues 198-222) from the full-length Brachyury protein to create a deletion mutant (amino acid residues 1-197 and 223-435). This extracted removal approach eliminates the harmful DNA binding activity while preserving the immunogenic epitopes, thereby resolving the contradiction between inducing immune response and maintaining DNA binding function.
Solution Approach 2:
The patent applies local quality modification by specifically altering only the DNA binding domain region while preserving other regions of the Brachyury protein that contain immunogenic epitopes. The deletion mutant maintains local immunogenic properties in regions 1-197 and 223-435 while removing the harmful local function in region 198-222, thus resolving the contradiction between immune response induction and DNA binding activity.
2Object-affected harmful factors
If Brachyury deletion mutant is used as cancer target, then tumor progression is inhibited, but malignant transformation function is compromised
Solution Approach 1:
The patent converts the harmful overexpression of Brachyury in cancer cells into a beneficial immunotherapeutic target. By using the Brachyury deletion mutant as a vaccine antigen, the normally harmful protein (which drives tumor progression when overexpressed) is transformed into a tool for inducing anti-tumor immunity. The mutant protein loses its harmful DNA binding function but retains its ability to elicit immune response against Brachyury-expressing tumor cells.
Data Source
AI summary
The invention provides Brachyury deletion mutant polypeptides, nucleic acids encoding the polypeptides, non-yeast vectors comprising the nucleic acids, non-yeast cells, and methods of use.