Tumor Lymphatic Targeting Peptides for Selective Metastasis Inhibition

Solution Overview

Problem

Conventional therapies struggle to effectively target and treat tumor lymphatic vasculature and metastasis due to the inaccessibility of hypoxic/nutrient-deprived regions in tumors, where the gC1q/p32 receptor is highly expressed, and existing targeting agents lack specificity for normal tissues.

Innovation Solution

Development of peptides and peptidomimetics, such as KRGARST, AKRGARSTA, and CKRGARSTC, that selectively home to tumor lymphatic vasculature, conjugated with therapeutic agents or detectable moieties, to target and reduce tumor lymphatic vessels and inhibit metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional therapies are used to treat tumors, then general tumor cells may be affected, but they cannot effectively target hypoxic/nutrient-deprived regions where the gC1q/p32 receptor is highly expressed

Engineering Contradiction:

Improvetargeting specificityVSAvoidinaccessibility of target region

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent applies local quality by designing a targeting system that specifically recognizes and binds to the gC1q/p32 receptor which is highly expressed in hypoxic/nutrient-deprived regions of tumors. The anti-gC1q/p32 antibody provides localized targeting precision to these specific microenvironments within the tumor, distinguishing them from well-perfused regions and normal tissues.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses an anti-gC1q/p32 antibody as an intermediary molecule that mediates the connection between the therapeutic delivery system and the target cells. This antibody specifically binds to the gC1q/p32 receptor on tumor cells in hypoxic regions, enabling selective delivery of therapeutic agents to these inaccessible areas.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If existing targeting agents are used, then some tumor tissue may be reached, but they lack specificity for normal tissues and cannot effectively inhibit metastasis

Engineering Contradiction:

Improvetreatment efficacyVSAvoidlack of specificity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing a targeting system that specifically recognizes and binds to the gC1q/p32 receptor which is highly expressed in hypoxic/nutrient-deprived regions of tumors. The anti-gC1q/p32 antibody provides localized targeting precision to these specific microenvironments within the tumor, distinguishing them from well-perfused regions and normal tissues.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses an anti-gC1q/p32 antibody as an intermediary molecule that mediates the connection between the therapeutic delivery system and the target cells. This antibody specifically binds to the gC1q/p32 receptor on tumor cells in hypoxic regions, enabling selective delivery of therapeutic agents to these inaccessible areas.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If high doses of therapeutic agents are administered to overcome resistance, then treatment coverage increases, but toxicity to normal tissues increases

Engineering Contradiction:

Improvetreatment coverageVSAvoidtoxicity to normal tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an anti-gC1q/p32 antibody as an intermediary molecule that mediates the connection between the therapeutic delivery system and the target cells. This antibody specifically binds to the gC1q/p32 receptor on tumor cells in hypoxic regions, enabling selective delivery of therapeutic agents to these inaccessible areas.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent segments the tumor microenvironment by targeting specific hypoxic/nutrient-deprived regions that express the gC1q/p32 receptor, rather than treating the entire tumor uniformly. This allows concentrated therapeutic effect in the most resistant regions while sparing normal tissues through selective targeting.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250361270A1Targeted delivery system and methods of use therefor

Publication Date: 2025.11.27 SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INST

AI summary

Disclosed are peptides and peptidomimetics that in some embodiments include the amino acid sequence KRGARST or (SEQ ID NO: 1), AKRGARSTA or (SEQ ID NO: 2), or CKRGARSTC (SEQ ID NO: 3). Also disclosed are conjugates and compositions that include the peptides and/or peptidomimetics, methods for directing a moiety to tumor lymphatic vasculature, methods for imaging tumor lymphatic vasculature, methods for reducing or inhibiting tumor metastasis, methods for reducing the number of tumor lymphatic vessels, methods for treating cancer, methods for treating a disease or disorder associated with a gC1q/p32 receptor biological activity, methods for detecting the presence of a gC1q/p32 receptor, methods for detecting interactions between gC1q/p32 receptors and the presently disclosed conjugates and compositions, methods for delivering the presently disclosed conjugates and compositions to gC1q/p32 receptors, methods for assessing gC1q/p32 receptor levels in cells, methods for identifying subjects having diseases associated with gC1q/p32 receptor biological activities, and methods for screening for compounds that interact with gC1q/p32 receptors.