TRAC-Deleted UCART22 Cells for Refractory CD22+ Cancer

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Solution Overview

Problem

Current immunotherapy methods using CAR-expressing T cells face challenges such as inefficiency in the presence of anti-T cell drugs, persistence issues, and the ability to target cancer cells that downregulate surface antigens recognized by CARs, leading to potential escape from treatment and adverse effects like cytokine release syndrome.

Innovation Solution

Development of engineered primary human T cells, specifically UCART22, which have a deletion of the TRAC gene and express a chimeric antigen receptor (CAR) targeting CD22. These cells also include a safety marker for in vivo control and have additional deletions in genes like CD52, dCK, or β2 Microglobulin to enhance their therapeutic efficacy and safety.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-expressing T cells are used for immunotherapy, then cancer cells can be targeted and destroyed, but the cells may be killed by anti-T cell drugs and cannot persist

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidsensitivity to anti-T cell drugs

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes the TRAC gene (encoding the T cell receptor alpha chain) from the T cells, extracting the component that makes them sensitive to anti-T cell drugs. This allows the CAR-expressing T cells to escape the harmful effect of anti-T cell drugs while maintaining their cancer-targeting capability through the CAR

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The TRAC gene deletion is performed in advance during the engineering of CAR-T cells, before the cells are administered to patients. This preliminary genetic modification ensures that the T cells are pre-equipped with resistance to anti-T cell drugs from the start of therapy

Inventive Principle:

Principle #10Preliminary action

2Reliability

If CAR-expressing T cells are used for immunotherapy, then cancer cells can be targeted, but cytokine release syndrome and graft versus host disease occur

Engineering Contradiction:

Improveanti-cancer activityVSAvoidcytokine release syndrome

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the genetic parameters of the T cells by deleting the TRAC gene and incorporating the CAR construct. This parameter change in the T cell genome leads to reduced cytokine production and lower incidence of cytokine release syndrome and graft versus host disease, while maintaining anti-cancer activity

Inventive Principle:

Principle #35Parameter changes

3Productivity

If CAR-expressing T cells are used for immunotherapy, then cancer treatment can be administered, but the cells cannot be controlled in vivo

Engineering Contradiction:

Improvetherapeutic activityVSAvoidin vivo control

Core Design Contradiction:

ProductivityVSEase of operation

Solution Approach 1:

The patent incorporates a safety switch mechanism that provides feedback control over T cell activity. This allows in vivo control of the CAR-expressing T cells by activating or deactivating the CAR expression based on therapeutic needs, enabling both high productivity when needed and easy control when required

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20250026808A1Universal Anti-CD22 chimeric antigen receptor engineered immune cells

Publication Date: 2025.01.23 CELLECTIS SA

AI summary

The present invention relates to an engineered immune cell endowed with a new CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect said immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.