Trifunctional Constructs for Tumor Targeting and Reduced Off-Target Binding

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Solution Overview

Problem

Existing anti-tumor therapies face challenges in achieving targeted delivery to tumors with minimal binding to non-target tissues, leading to increased side effects and reduced efficacy.

Innovation Solution

Development of multi-targeted compounds with distinct affinity domains for human serum albumin and tumor-specific markers, allowing for increased tumor perfusion and uptake while minimizing non-target binding, incorporating therapeutic agents like toxins or radionuclides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-tumor therapies are used, then treatment is provided, but binding to non-target tissues increases side effects and reduces efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidside effects from non-target binding

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The compound is divided into separate functional domains: an albumin-binding domain (increases circulation time) and a tumor-binding domain (provides targeted delivery). This segmentation allows each domain to perform its specific function independently, improving both circulation residence time and target specificity while reducing non-target tissue binding.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different regions of the compound have different binding affinities and functions. The albumin-binding domain has high affinity for albumin (KD = 0.25-50 µM) to extend circulation, while the tumor-binding domain has high affinity for tumor-specific markers (KD = 0.1-75 nM) for targeted delivery. This local differentiation of binding properties enables selective accumulation in tumors while minimizing non-target binding.

Inventive Principle:

Principle #3Local quality

2Quantity of substance

If compounds with high tumor affinity are used, then tumor uptake increases, but circulatory residence time decreases

Engineering Contradiction:

Improvetumor uptakeVSAvoidcirculatory residence time

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The albumin-binding domain enables the compound to circulate longer in the bloodstream before reaching the tumor, allowing more time for the compound to accumulate in the tumor tissue. This preliminary extension of circulatory residence time enhances the quantity of compound available for tumor uptake.

Inventive Principle:

Principle #10Preliminary action

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

Enhanced tumor uptake and retention, reduced non-target binding, and improved therapeutic efficacy by utilizing compounds with differential affinities for albumin and tumor-specific targets, thereby increasing treatment effectiveness and minimizing side effects.

Implementation Method 1

an albumin-binding domain, having specific affinity for binding human serum albumin in the range of about 0.25 to 50 micromolar

Methodology Applied

Scientific EffectProtein-protein binding: Adsorption

Implementation Method 2

a tumor-binding domain having specific affinity for a tumor associated molecular target in the range of about 0.1 to 75 nanomolar

Methodology Applied

Scientific EffectLigand-receptor binding: Adsorption

Implementation Method 3

an auger electron-emitting radionuclide, a beta-emitting radionuclide, or an alpha-emitting radionuclide

Methodology Applied

Scientific EffectIonizing radiation: Radiation

Data Source

PatentUS12377175B2Trifunctional constructs with tunable pharmacokinetics useful in imaging and anti-tumor therapies

Publication Date: 2025.08.05 CORNELL UNIVERSITY

AI summary

The present technology provides compounds, as well as compositions including such compounds, useful for imaging and/or treatment of a glioma, a breast cancer, an adrenal cortical cancer, a cervical carcinoma, a vulvar carcinoma, an endometrial carcinoma, a primary ovarian carcinoma, a metastatic ovarian carcinoma, a non-small cell lung cancer, a small cell lung cancer, a bladder cancer, a colon cancer, a primary, gastric adenocarcinoma, a primary colorectal adenocarcinoma, a renal cell carcinoma, and/or a prostate cancer.