Chimeric Antigen Receptor Protease Cleavage Site for Myeloid Cell Activation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for activating myeloid cells in vivo for targeted therapy, such as cancer treatment, face challenges in precise activation and control, leading to potential persistent inflammation or unresponsive immune cells.

Innovation Solution

A recombinant polynucleic acid composition encoding a chimeric antigen receptor (CAR) with a protease cleavage site allows for tunable activation of myeloid cells by releasing a transcription factor upon antigen binding, enabling targeted cytotoxicity and controlled immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If myeloid cells are activated in vivo for targeted therapy, then cytotoxicity against disease-causing cells is enhanced, but persistent inflammation occurs

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpersistent inflammation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent incorporates a protease cleavage site into the chimeric antigen receptor construct before administration, pre-positioning a regulatory mechanism that will automatically control transcription factor release and prevent persistent inflammation during in vivo activation of myeloid cells

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs a feedback mechanism where protease activity (such as TMPRSS2 or HTRA1) automatically regulates the release of the transcription factor from the chimeric antigen receptor, creating a self-regulating system that enhances cytotoxicity while preventing persistent inflammation through endogenous control

Inventive Principle:

Principle #23Feedback

2Reliability

If myeloid cells are activated for targeted therapy, then cytotoxicity is enhanced, but immune cell responsiveness becomes uncontrolled

Engineering Contradiction:

Improvetargeted cytotoxicityVSAvoidimmune cell responsiveness

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the activation parameter of myeloid cells from constitutive transcription factor expression to protease-dependent release, allowing controlled immune cell responsiveness while maintaining targeted cytotoxicity through regulation of transcription factor availability

Inventive Principle:

Principle #35Parameter changes

3Reliability

If a transcription factor is continuously expressed in myeloid cells, then cytotoxicity is maintained, but precise activation control is lost

Engineering Contradiction:

ImprovecytotoxicityVSAvoidactivation control

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent segments the chimeric antigen receptor construct into distinct functional domains including a protease cleavage site that separates the transcription factor from the membrane anchor, enabling precise activation control while maintaining cytotoxicity through regulated transcription factor release upon protease cleavage

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20240139314A1Engineered chimeric fusion protein compositions and methods of use thereof

Publication Date: 2024.05.02 MYELOID THERAPEUTICS INC

AI summary

The present disclosure provides compositions and methods for making and using engineered myeloid cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, wherein the chimeric receptor is encoded by a recombinant nucleic acid.