CD21-Targeting CAR T-Cell Therapy for T-ALL

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Solution Overview

Problem

Current therapies for T-cell acute lymphocytic leukemia (T-ALL) are limited, as targeting pan-T-cell antigens leads to unacceptable immunosuppression, and existing CAR T-cell therapies are not effective for T-ALL due to fratricide of normal T-cells.

Innovation Solution

Development of a chimeric antigen receptor (CAR) with a CD21-binding domain, a transmembrane domain, and an intracellular signaling domain, which can specifically target CD21-expressing T-ALL cells without causing significant immunosuppression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pan-T-cell antigens are targeted for CAR T-cell therapy, then T-ALL cells can be killed, but profound immunosuppression occurs which cannot be mitigated

Engineering Contradiction:

Improvekilling efficacy against T-ALLVSAvoidimmunosuppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by selecting a specific antigen (CD21) that is locally expressed on T-ALL cells but not on normal T-cells. The CAR T-cells are engineered with CD21-specific binding domains (anti-CD21 scFv) that confer selective recognition capability, enabling the therapy to act locally on malignant cells while sparing normal immune cells, thus achieving effective tumor killing without systemic immunosuppression

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent segments the T-cell population by targeting a specific antigen expression pattern. Normal T-cells lack CD21 expression and are therefore segmented out from the therapy's effect, while T-ALL cells expressing CD21 are selectively targeted. This segmentation allows the therapy to distinguish between malignant and normal cells, avoiding the harmful immunosuppression that would result from targeting pan-T-cell antigens

Inventive Principle:

Principle #1Segmentation

2Ease of manufacture

If normal T-cells express the target molecule, then CAR T-cell production can proceed, but fratricide of normal T-cells occurs

Engineering Contradiction:

ImproveCAR T-cell productionVSAvoidfratricide of normal T-cells

Core Design Contradiction:

Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent employs local quality by engineering CAR T-cells with CD21-specific binding domains that confer selective recognition capability. Since normal T-cells do not express CD21, they are not recognized or attacked by the CAR T-cells, eliminating fratricide. The therapy's effect is localized to CD21-expressing T-ALL cells while normal T-cells remain unaffected and can be used for CAR T-cell production

Inventive Principle:

Principle #3Local quality

3Reliability

If CD19 is targeted for CAR T-cell therapy, then remission rates improve, but the normal B-cell compartment is lost

Engineering Contradiction:

Improveremission rateVSAvoidnormal B-cell compartment

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies inversion by switching from targeting a B-cell antigen (CD19) to targeting a T-cell leukemia antigen (CD21). This inversion allows the therapy to be effective against T-ALL while sparing the B-cell compartment. The CAR T-cells are engineered to recognize CD21 on T-ALL cells, achieving remission in T-ALL patients without the harmful effect of depleting normal B-cells

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS12209114B2Chimeric antigen receptor

Publication Date: 2025.01.28 UCL BUSINESS LTD

AI summary

The present invention provides a chimeric antigen receptor (CAR) comprising a CD21-binding domain, a transmembrane domain and an intracellular domain.