Cbl-b Knockout Tumor-Inhibiting Cells Against TGF-β Suppression

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Solution Overview

Problem

Existing immunotherapy approaches for treating tumors face limitations such as immune evasion mechanisms, specificity issues, and effectiveness in only certain types of cancers, leading to transient effects and potential autoimmune disorders.

Innovation Solution

Development of Cbl-b−/− tumor inhibiting cells (TICs) modified from immune cells with inactivated Cbl-b genomic alleles, free from exogenous DNA and viral nucleic acids, to enhance tumor-specific cytotoxicity and resistance to TGF-β suppression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immune cells are transferred back to the patient for tumor treatment, then the immune system can target tumor cells, but the hostile tumor environment disables the immune cells' tumor killing potency

Engineering Contradiction:

Improvetumor killing potencyVSAvoidhostile tumor environment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by inactivating the Cbl-b gene in immune cells before transferring them to the patient. This pre-modification prevents the tumor environment from suppressing the immune cells' cytotoxic function, as the Cbl-b protein that would normally mediate TGF-β-induced suppression is non-functional. The immune cells are prepared in advance to resist the hostile tumor microenvironment.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent changes the genetic parameter of the immune cells by inactivating the Cbl-b gene. This genetic modification alters the cells' response properties to TGF-β, transforming them from being suppressible by the tumor environment to being resistant. The parameter change occurs at the molecular level, affecting the signaling pathway that controls cytotoxic function.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If CAR-T receptors are used to recognize tumor antigens, then targeted therapy is achieved, but tumor cells can lose the specific epitope and escape treatment

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtumor epitope recognition

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of modifying the immune cells to recognize a single tumor epitope (CAR-T approach), the patent inverts the strategy by modifying the immune cells' susceptibility to suppression. Rather than making the recognition specific and narrow, the approach makes the functional response broad and resistant, allowing the immune cells to maintain cytotoxicity against tumors regardless of epitope heterogeneity or loss.

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If gene modification is applied to enhance immune cell function, then tumor inhibition is improved, but exogenous DNA and viral nucleic acids may remain in the modified cells

Engineering Contradiction:

Improvetumor inhibition efficacyVSAvoidexogenous DNA and viral nucleic acids

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies the extraction principle by removing exogenous genetic material from the modified immune cells. After inactivating the Cbl-b gene through transient transfection, the cells are cultured and selected to eliminate plasmid DNA and viral vectors. The final product contains only the desired genetic modification (Cbl-b inactivation) without residual exogenous DNA or viral nucleic acids, achieving both efficacy and safety.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12569516B2Subject-specific tumor inhibiting cells and the use thereof

Publication Date: 2026.03.10 EZY BIOTECH LLC

AI summary

This disclosure is directed to a pharmaceutical composition comprises tumor inhibiting cells (TICs) and a method for producing the TICs. The tumor inhibiting cells can be derived from immune cells including T cells, NK cells, or a combination thereof, modified to have inactivated Cbl-b gene alleles and free from Cbl-b bio-function (Cbl-b−/− TICs). The Cbl-b−/− TICs are free from deoxyribonucleic acids exogenous to the immune cells. The immune cells can be isolated using a portable cell isolation and modification device. This disclosure is further directed to a method for treating tumorous conditions in subjects. The pharmaceutical composition can provide a subject-specific tumor treatment.