Mutant p53 TCRs for Targeting Unresectable Cancers
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Solution Overview
Problem
Current cancer treatments, such as surgery, chemotherapy, and radiation therapy, offer limited options for metastatic and unresectable cancers like pancreatic, colorectal, lung, endometrial, ovarian, and prostate cancers, resulting in poor prognosis for many patients.
Innovation Solution
Development of isolated or purified T cell receptors (TCRs) with antigenic specificity for human p53 mutations, specifically p53C135Y, p53R175H, and p53M237I, which can recognize and target cancer cells expressing these mutations, thereby inducing an immune response and potentially treating or preventing cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments (surgery, chemotherapy, radiation therapy) are used, then treatment options are available, but the prognosis remains poor for metastatic and unresectable cancers
Solution Approach 1:
The patent changes the fundamental parameter of cancer treatment from non-specific conventional therapies to highly specific T cell receptors that recognize unique mutant p53 peptides. This specificity parameter improvement enables targeted therapy for metastatic and unresectable cancers that previously had limited options, directly addressing the contradiction between treatment versatility and prognosis.
2Measurement precision
If T cell receptors with high specificity for mutant p53 are developed, then cancer cells can be specifically targeted, but the complexity of the treatment increases
Solution Approach 1:
The patent extracts the specific function of recognizing mutant p53 from the complex immune system and encapsulates it in isolated T cell receptor molecules. By taking out only the essential antigen-binding function and removing unnecessary complexity, the treatment achieves high specificity while simplifying the overall therapeutic approach.
Solution Approach 2:
The patent creates synthetic copies of naturally occurring T cell receptors that specifically bind to mutant p53 peptides. These engineered TCR copies can be produced recombinantly and used therapeutically, achieving high measurement precision (specificity) through molecular copying rather than requiring complex whole-cell therapies.
3Adaptability or versatility
If TCRs are used to target unmanipulated tumor cells, then more patients become eligible for immunotherapy, but the difficulty of detecting and measuring tumor-specific antigens increases
Solution Approach 1:
The patent performs preliminary identification and characterization of mutant p53 peptides that are presented on the surface of tumor cells before developing the TCR therapy. By预先 identifying the target antigens and validating their presence on unmanipulated tumor cells, the patent enables patient eligibility expansion while managing the detection challenge through advance preparation.
Data Source
AI summary
Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53C135Y, human p53R175H, or human p53M237I. 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.