Mutant p53-Specific T Cell Receptors for Targeted Cancer Killing
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Solution Overview
Problem
There are limited treatment options for cancers with metastasis, particularly for cancers like pancreatic, colorectal, lung, endometrial, ovarian, and prostate cancers, which often have poor prognosis despite existing treatments such as surgery, chemotherapy, and radiation therapy.
Innovation Solution
Development of isolated or purified T cell receptors (TCRs) with antigenic specificity for human p53R175H or human p53Y220C mutations, which can be used to induce an immune response against cancer cells expressing these mutations, including recombinant expression vectors and host cells to produce and administer these TCRs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies (surgery, chemotherapy, radiation therapy) are used to treat metastatic cancers, then some treatment effect is achieved, but the prognosis remains poor and treatment options are limited
Solution Approach 1:
The patent changes the fundamental parameter of cancer treatment from non-specific conventional therapies to highly specific T cell receptors targeting mutated p53 proteins. This parameter change enables selective recognition of cancer cells with specific mutations (R175H or Y220C) while sparing normal cells, thereby improving treatment effectiveness and providing a new therapeutic approach for metastatic cancers with poor prognosis
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 p53. These TCRs serve as specialized mediators that bridge the gap between the immune system and cancer cells, enabling targeted destruction of malignant cells while preserving normal tissue
2Object-affected harmful factors
If T cell receptors with high specificity for mutated p53 are developed, then cancer cells are specifically targeted, but the complexity of identifying and producing these TCRs increases
Solution Approach 1:
The patent extracts and isolates specific T cell receptor sequences that recognize mutated p53 from complex immune responses. By identifying and separating the functional TCR components (with specific amino acid sequences in CDR regions) from the overall immune system complexity, the invention enables targeted production of these receptors through recombinant expression systems, thereby reducing the practical complexity of manufacturing while maintaining high specificity
Solution Approach 2:
The patent creates copies of identified TCR sequences through recombinant expression in host cells. Once the functional TCR sequences are identified, they can be replicated and produced in large quantities through cellular copying mechanisms, simplifying the production process while ensuring consistent specificity and activity
Data Source
AI summary
Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53R175H or human p53Y220C. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.