DLL3/CD3 Antigen-Binding Molecule for SCLC T-Cell Targeting

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Solution Overview

Problem

Small cell lung cancer (SCLC) lacks specific targeted therapy drugs, and existing immunotherapies like PD-L1 and PD1 antibodies have limited efficacy and are associated with severe cytokine release syndrome due to anti-CD3 antibody administration.

Innovation Solution

Development of an antigen-binding molecule that specifically binds to DLL3 and CD3, comprising specific heavy and light chain variable regions, to target SCLC cells and activate T-cells without triggering excessive cytokine release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-CD3 antibodies are administered to activate T cells for cancer treatment, then T cell activation and cancer treatment efficacy are improved, but severe cytokine release syndrome occurs

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidcytokine release syndrome

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces DLL3 as an intermediary target on tumor cells. The anti-CD3 antibody is modified to include a DLL3 binding domain, creating a bridge that directs T cell activation specifically to tumor cells expressing DLL3. This intermediary mechanism reduces off-target T cell activation and subsequent cytokine release syndrome while maintaining anti-tumor efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies local quality by making the antibody's antigen-binding properties location-specific. The modified antibody only activates T cells in proximity to DLL3-expressing tumor cells, rather than systemically activating T cells throughout the body. This localized activation approach reduces the harmful cytokine release syndrome while preserving cancer treatment efficacy.

Inventive Principle:

Principle #3Local quality

2Productivity

If chemotherapy drugs are used to treat small cell lung cancer, then initial treatment response is improved, but drug resistance and relapse occur

Engineering Contradiction:

Improvetreatment response rateVSAvoidlong-term treatment efficacy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the fundamental parameter of treatment mechanism from chemotherapy (cell division inhibition) to immunotherapy (T cell-mediated cytotoxicity). The modified anti-CD3 antibody with DLL3 binding domain recruits and activates patient's own T cells to kill tumor cells, providing a different mode of action that can overcome chemotherapy-induced resistance and achieve sustained long-term responses.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If PD-L1 or PD1 antibodies are used for immunotherapy in SCLC, then some efficacy is achieved, but the effective rate is limited at about 15%

Engineering Contradiction:

Improveimmunotherapy efficacyVSAvoideffective rate

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent segments the immunotherapy approach by first targeting DLL3 to recruit T cells to the tumor microenvironment, then engaging CD3 to activate them. This two-step segmented mechanism ensures both T cell presence and activation, overcoming the limited efficacy of single-target PD-1/PD-L1 blockade and achieving higher effective rates in SCLC treatment.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250376519A1Antigen-binding molecule specifically binding to DLL3 and CD3, and pharmaceutical use thereof

Publication Date: 2025.12.11 JIANGSU HENGRUI MEDICINE CO LTD

AI summary

The present disclosure relates to an antigen-binding molecule specifically binding to DLL3 and CD3, and pharmaceutical use thereof. The antigen-binding molecule can be used for treating cancers.