TIM3-Binding CARs for Targeted T Cell Therapy

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Solution Overview

Problem

Current cancer therapies, including surgery, radiation, and chemotherapy, have limitations in effectively targeting and eliminating TIM3-expressing cancers, as they do not fully harness the immune system's potential for cancer treatment.

Innovation Solution

Development of chimeric antigen receptors (CARs) with an anti-TIM3 binding agent, such as antibody fragments or aptamers, that can be used in adoptive cell transfer to specifically target and kill TIM3-expressing cancer cells, combined with immune effector cells like T cells engineered to express these CARs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer therapies (surgery, radiation, chemotherapy) are used, then treatment can be provided, but they cannot effectively target and eliminate TIM3-expressing cancers due to inability to harness immune system potential

Engineering Contradiction:

Improveeffectiveness of cancer treatmentVSAvoidability to target TIM3-expressing cancers

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces chimeric antigen receptors (CARs) as intermediary structures that bridge the immune system and TIM3-expressing cancer cells. These CARs consist of an anti-TIM3 binding agent (antibody fragment or aptamer) that specifically recognizes TIM3 on cancer cells, coupled to signaling domains that activate immune effector cells. This intermediary structure enables conventional immune cells to specifically target and eliminate TIM3-expressing cancers that were previously resistant to treatment.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If the immune system is harnessed for cancer therapy, then effective treatment can be developed, but current immunotherapy approaches do not sufficiently target TIM3-expressing cancers

Engineering Contradiction:

Improveimmunosystem's potential for cancer treatmentVSAvoideffectiveness against TIM3-expressing cancers

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by engineering immune effector cells with CARs that have specific local functionality - the anti-TIM3 binding agent portion of the CAR is designed to specifically recognize and bind to TIM3 molecules on the surface of cancer cells. This localized specificity ensures that the immune response is precisely directed at TIM3-expressing cancers while sparing other cells, thereby enhancing both the adaptability and reliability of immunotherapy for this specific cancer type.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If chimeric antigen receptors with anti-TIM3 binding agents are developed, then specific targeting of TIM3-expressing cancer cells is achieved, but complexity of the therapy increases

Engineering Contradiction:

Improvespecificity to TIM3-expressing cancersVSAvoidcomplexity of CAR structure and therapy

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The CAR structure is segmented into distinct functional domains: an ectodomain containing the anti-TIM3 binding agent (which may be an antibody fragment like scFv or an aptamer), a transmembrane domain, and endodomains containing signaling regions. This segmentation allows each component to perform its specific function while maintaining overall structural organization. The binding agent segment specifically recognizes TIM3, the transmembrane segment anchors the CAR in the immune cell membrane, and the endodomains transmit activation signals, thereby managing complexity through functional modularity.

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The CARs enable targeted anti-tumor immunity by binding to TIM3-expressing cancer cells, activating immune effector cells to kill cancer cells, thereby providing an effective treatment for TIM3-expressing cancers like acute myeloid leukemia.

Implementation Method 1

an anti-TIM3 binding agent that can bind TIM3-expressing cancer cells

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

The anti-TIM3 binding agent can be an aptamer that specifically binds TIM3

Methodology Applied

Scientific EffectAptamer binding:

Data Source

PatentUS11458169B2TIM3-binding chimeric antigen receptors

Publication Date: 2022.10.04 H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE INC

AI summary

Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill TIM3-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a TIM3-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.