KRAS G12D-Specific T Cell Receptors for Targeted Cancer Killing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There are limited treatment options for metastatic and unresectable cancers such as pancreatic, colorectal, lung, endometrial, ovarian, and prostate cancers, with poor prognosis despite existing treatments like surgery, chemotherapy, and radiation therapy.

Innovation Solution

Development of isolated or purified TCRs with antigenic specificity for mutated KRAS, particularly the G12D mutation, which can recognize KRAS within the context of HLA-Cw8 or HLA-Cw5 molecules, enabling targeted destruction of cancer cells while minimizing harm to normal cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapies (surgery, chemotherapy, radiation therapy) are used to treat metastatic and unresectable cancers, then treatment options are available, but the prognosis remains poor and treatment effectiveness is limited

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtreatment option availability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of treatment approach by shifting from conventional cytotoxic therapies to immunotherapy using engineered TCRs. This involves changing the mechanism of action from direct cell killing to immune system-mediated targeting, thereby improving treatment effectiveness for metastatic cancers while expanding therapeutic options

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces TCR-engineered T cells as an intermediary between the patient's immune system and cancer cells. These engineered T cells serve as mediators that specifically recognize and target mutated KRAS on cancer cells, enabling effective treatment of metastatic diseases that are resistant to conventional therapies

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If TCRs with high specificity for mutated KRAS are developed to target cancer cells, then treatment precision is improved, but the complexity of developing and implementing this therapy increases

Engineering Contradiction:

Improvetargeting specificityVSAvoidtherapy development complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the antigen recognition function from the entire T cell and isolates it into a specific TCR component that targets mutated KRAS. This extracted TCR can then be engineered into patient's T cells, separating the complex development process into manageable steps: TCR identification, engineering, and cellular therapy implementation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the immunotherapy approach into distinct components: (1) identification of specific TCR sequences that recognize mutated KRAS, (2) engineering these TCRs into T cells, and (3) administering the engineered cells. This segmentation allows systematic development and optimization of each component separately

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250340611A1Anti-KRAS-g12d t cell receptors

Publication Date: 2025.11.06 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented in the context of an HLA-Cw*0802 molecule. 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.