EGFR-Targeted Chimeric Peptide for Cancer Therapy

Solution Overview

Problem

Current cancer therapies using bacterial toxin-based immunotoxins face limitations due to liver toxicity, immunogenicity, and poor penetration of large molecular size into tumor masses, necessitating the development of new generation immunotoxins with improved targeting and reduced toxicity.

Innovation Solution

A chimeric peptide, EGFR-targeted peptidetoxin, is developed, comprising a receptor-binding peptide and a cytotoxic lytic peptide with a spacer, which is stable and exhibits reduced toxicity to normal cells, enhancing cell-killing efficacy specifically in cancer cells by targeting EGFR-overexpressing cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If bacterial toxin-based immunotoxins are used for cancer therapy, then cancer cell targeting is achieved, but liver toxicity and immunogenicity occur

Engineering Contradiction:

Improvecancer cell targetingVSAvoidliver toxicity and immunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The immunotoxin is divided into separate functional modules: a targeting moiety (monoclonal antibody or ligand) and a cytotoxic moiety (bacterial toxin). This segmentation allows independent optimization of targeting specificity and cytotoxic activity while reducing systemic toxicity through controlled delivery to cancer cells

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A linking moiety serves as an intermediary between the targeting moiety and cytotoxic moiety, enabling controlled spatial arrangement and orientation of the immunotoxin components. This intermediary structure optimizes the distance and geometry for effective cancer cell binding and toxin delivery while minimizing off-target effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If large molecular size immunotoxins are used, then cancer cell targeting is improved, but penetration into tumor mass is reduced

Engineering Contradiction:

Improvecancer cell targetingVSAvoidmolecular size

Core Design Contradiction:

ReliabilityVSLength of moving object

Solution Approach 1:

The immunotoxin is divided into separate functional modules: a targeting moiety (monoclonal antibody or ligand) and a cytotoxic moiety (bacterial toxin). This segmentation allows independent optimization of targeting specificity and cytotoxic activity while reducing systemic toxicity through controlled delivery to cancer cells

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The molecular parameters of the immunotoxin are optimized by selecting appropriate linking moiety lengths and compositions. This parameter adjustment balances the need for sufficient targeting affinity with the requirement for adequate tumor mass penetration, allowing the immunotoxin to navigate through extracellular matrix barriers

Inventive Principle:

Principle #35Parameter changes

3Productivity

If lytic peptides are used for cancer cell membrane disruption, then cell-killing efficacy is improved, but toxicity to normal cells increases

Engineering Contradiction:

Improvecell-killing efficacyVSAvoidtoxicity to normal cells

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The lytic peptide is confined to act locally at the cancer cell membrane through specific targeting. The targeting moiety directs the lytic peptide to cancer cells expressing specific surface markers, ensuring that membrane disruption occurs only at the intended target site and not in surrounding normal tissues

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

A linking moiety serves as an intermediary between the targeting moiety and cytotoxic moiety, enabling controlled spatial arrangement and orientation of the immunotoxin components. This intermediary structure optimizes the distance and geometry for effective cancer cell binding and toxin delivery while minimizing off-target effects

Inventive Principle:

Principle #24Intermediary (Mediator)

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 EGFR-targeted peptidetoxin demonstrates significant antitumor activity, inducing rapid cell death and apoptosis in cancer cells with lower IC50 values compared to lytic peptides alone, while maintaining low toxicity to normal cells, thus offering a novel targeted therapy for cancer.

Implementation Method 1

Selective anticancer chimeric peptides which bind transferrin receptor

Methodology Applied

Scientific EffectReceptor-ligand binding:

Implementation Method 2

cytotoxic lytic peptide with a spacer, which is stable and exhibits reduced toxicity to normal cells, enhancing cell-killing efficacy specifically in cancer cells

Methodology Applied

Scientific EffectMembrane lysis:

Data Source

PatentUS8940862B2Selective anticancer chimeric peptides which bind transferrin receptor

Publication Date: 2015.01.27 STELLA PHARMA CORPORATION

AI summary

It is an object of the present invention to provide a substance usable as an anticancer agent or DDS, which has intracellular stability, which is capable of evading side effects from functional disorder with respect to normal cells, or which has instantaneous effect. The inventors developed a novel chimeric peptide targeting cancer cells which overexpress EGFR or the like using a binding peptide such as a peptide sequence binding to EGFR, and a lytic peptide sequence, thereby solving such an object. Particularly, by using a chimeric peptide including an EGF receptor-binding peptide or the like and a cytotoxic peptide, this object was solved.