T Cell Receptors Targeting Mutated p53 R273C Y220C

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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, necessitating the development of additional therapeutic approaches.

Innovation Solution

Development of isolated or purified T cell receptors (TCRs) with antigenic specificity for mutated human p53 sequences, specifically p53R273C and p53Y220C, to induce an immune response and target cancer cells while minimizing damage to normal cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional cancer treatments (surgery, chemotherapy, radiation therapy) are used, then existing treatment options are applied, but treatment options are limited for metastatic and unresectable cancers

Engineering Contradiction:

Improvetreatment optionsVSAvoidprognosis

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent introduces T cell receptors (TCRs) with specific antigenic specificity for mutated p53 as an intermediary biological agent. These TCRs enable the immune system to specifically recognize and target cancer cells expressing mutated p53, bridging the gap between conventional treatments and the need for targeted immunotherapy in metastatic and unresectable cancers

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the therapeutic approach by shifting from non-specific conventional treatments to highly specific immunotherapy. By developing TCRs with antigenic specificity for particular p53 mutations (R273C, Y220C), the treatment parameters are optimized to target specific cancer cell populations while sparing normal cells, thereby expanding treatment options and improving prognosis

Inventive Principle:

Principle #35Parameter changes

2Reliability

If TCRs with antigenic specificity for mutated p53 are developed, then specific immune response is elicited against cancer cells, but treatment complexity increases

Engineering Contradiction:

Improvespecificity of immune responseVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates specific T cell receptors with antigenic specificity for mutated p53 from the complex immune system. By identifying and isolating TCRs that specifically recognize p53R273C or p53Y220C mutations, the invention simplifies the treatment approach by focusing on a specific molecular target rather than attempting to modulate the entire immune system

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The developed TCRs serve multiple functions: they can be used for diagnostic purposes to detect cancers with specific p53 mutations, for therapeutic purposes to elicit immune responses against tumor cells, and potentially for monitoring treatment response. This multi-functionality reduces overall treatment complexity by consolidating multiple clinical needs into a single therapeutic agent

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230321240A1T cell receptors recognizing r273c or y220c mutations in p53

Publication Date: 2023.10.12 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53R273C 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.