Humanized Anti-CD19 CAR T Cells for Durable B Cell Cancer Therapy

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Solution Overview

Problem

Existing cancer immunotherapy methods, such as chimeric antigen receptor (CAR) modified autologous T cell (CART) therapy, face challenges in achieving clinical effectiveness due to variable T cell quality, anergy, suppression, or exhaustion, leading to suboptimal persistence and proliferation of CAR-transformed T cells, especially in treating B cell malignancies.

Innovation Solution

Development of a humanized anti-CD19 chimeric antigen receptor (CAR) integrated into T cells, comprising optimized antibody fragments and intracellular signaling domains to enhance T cell persistence and proliferation, while minimizing immune response and maintaining clinical effectiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If murine derived CAR T cells are used to treat B cell malignancies, then complete remissions can be achieved, but the T cells may elicit an immune response in patients and have limited long-term safety

Engineering Contradiction:

Improveclinical effectivenessVSAvoidimmune response

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies humanization to modify the antibody sequence parameters, changing it from murine to human-derived sequences. This parameter change maintains the antigen-binding function while eliminating the immune response against the therapeutic T cells, thereby resolving the contradiction between clinical effectiveness and long-term safety.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a humanized version of the murine CAR by copying and modifying the antibody sequence. Instead of using the original murine sequence, a humanized copy is constructed that retains the functional properties while being immunologically compatible with human patients, thus resolving the immune response issue while maintaining effectiveness.

Inventive Principle:

Principle #26Copying

2Productivity

If T cells are engineered with CAR to recognize and destroy targeted cancer cells, then tumor cell destruction is enhanced, but T cell persistence and proliferation capability becomes variable and suboptimal

Engineering Contradiction:

Improvetumor cell destructionVSAvoidT cell persistence

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The patent optimizes the intracellular signaling domain parameters by selecting specific combinations of costimulatory and signaling domains (e.g., CD28/4-1BB, CD3zeta configurations). These parameter changes in the signaling architecture enhance both the immediate cytotoxic activity and the long-term persistence and proliferation of CAR T cells, resolving the contradiction between tumor destruction and sustained functionality.

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If standard therapy is used to treat B cell malignancies, then treatment can be administered, but serious side effects occur and clinical effectiveness is limited

Engineering Contradiction:

Improvetreatment availabilityVSAvoidside effects

Core Design Contradiction:

Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent replaces conventional chemical chemotherapy mechanisms with an immunological mechanism using engineered T cells. This substitution eliminates many of the serious side effects associated with standard chemotherapy while maintaining treatment availability, as the CAR T cell therapy targets cancer cells specifically through antigen recognition rather than non-specific chemical damage.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Adaptability or versatility

If hundreds of tumor antigens are used for cancer immunotherapy, then more target options are available, but the antigens are derived from self and thus are poorly immunogenic

Engineering Contradiction:

Improveantigen target optionsVSAvoidimmunogenicity

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent extracts the antigen-binding function from the context of self-antigens by using monoclonal antibodies that specifically recognize tumor-associated antigens like CD19. By isolating and utilizing these specific antibody-antigen interactions in a CAR construct, the therapy achieves high immunogenicity and effectiveness without relying on poorly immunogenic self-antigens, thus resolving the contradiction between target versatility and immunogenicity.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12606636B2Treatment of cancer using humanized anti-CD19 chimeric antigen receptor

Publication Date: 2026.04.21 NOVARTIS AG

AI summary

The invention provides compositions and methods for treating diseases associated with expression of CD19. The invention also relates to chimeric antigen receptor (CAR) specific to CD19, vectors encoding the same, and recombinant T cells comprising the CD19 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD19 binding domain.