Multi-target therapeutic constructs for cancer therapy

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Solution Overview

Problem

Current targeted cancer therapies face challenges in specificity and efficacy due to variable tumor cell surface targets and resistance mechanisms, leading to non-specific effects and reduced potency.

Innovation Solution

A construct comprising multiple peptides binding to different extracellular tumor antigens and a toxin, covalently bound directly or through a carrier, such as a PEG scaffold, to enhance targeting and cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single target is used for cancer therapy, then the therapy mechanism is simple, but the efficacy is reduced due to tumor cell variability and resistance mechanisms

Engineering Contradiction:

Improvetherapy efficacyVSAvoidconstruct structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple peptides targeting different tumor antigens (EGFR, PD-L1, HER2) into a single construct, along with multiple toxins (PE38, PE40), to create a multi-functional therapeutic agent that can simultaneously target multiple cancer cell pathways, thereby overcoming resistance mechanisms and improving efficacy

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The construct is designed with universal applicability by incorporating peptides that bind to multiple different tumor antigens and toxins that can kill various cancer cell types, making it effective against diverse cancer types and resistant cell lines

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Power

If multiple peptides and toxins are combined in a construct, then the cytotoxic potency is enhanced, but the manufacturing complexity increases

Engineering Contradiction:

Improvecytotoxic potencyVSAvoidconstruct synthesis

Core Design Contradiction:

PowerVSEase of manufacture

Solution Approach 1:

The construct is segmented into distinct functional modules: peptide binding domains (EGFR-targeting, PD-L1-targeting, HER2-targeting), toxin domains (PE38, PE40), and linker regions, allowing for modular assembly and simplified manufacturing through stepwise conjugation

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Linker molecules serve as intermediaries between the peptide binding domains and toxin domains, facilitating modular assembly and simplifying the conjugation process by providing standardized connection points

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If traditional chemotherapy is used, then the treatment covers all dividing cells, but the specificity is low causing non-specific killing of normal cells

Engineering Contradiction:

Improvecell targeting specificityVSAvoidkilling efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The construct exhibits local quality by concentrating cytotoxic activity specifically at tumor cell locations through peptide-mediated targeting, while leaving normal cells unaffected, thereby achieving both high specificity and high killing efficiency at the target site

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20240002547A1Therapeutic multi-targeting constructs and uses thereof

Publication Date: 2024.01.04 AEBI

AI summary

The present invention provides constructs comprising a plurality of peptides capable of targeting at least two different extracellular tumor antigens and a toxin, optionally connected to an organic scaffold. Use of such constructs in treating cancer are provided as well. The invention also provides particular peptides binding certain extracellular tumor antigens as well as toxins having antitumor activity.