PCNA-Targeting Peptide Composition for Soft Tissue Sarcoma Uptake
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Solution Overview
Problem
Existing APIM-peptides have shown limited efficacy in cancer therapies, particularly in human patients, and require higher concentrations than animal studies, with unclear intracellular persistence and effectiveness as single active agents.
Innovation Solution
A pharmaceutical composition comprising a peptide with a PCNA interacting motif (SEQ ID NO: 1) and a cell penetrating peptide, administered weekly at a dose of 15-65 mg/m² BSA, targets carcinomas and sarcomas by enhancing cellular uptake and providing long-term intracellular action.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If APIM-peptides are administered alone in animal studies, then they show limited anti-cancer activity, but they require high concentrations and do not persist intracellularly
Solution Approach 1:
The patent combines the APIM-peptide sequence with a cell-penetrating peptide (CPP) to create a composite peptide molecule. This composite structure enables the peptide to effectively enter cells and persist intracellularly, achieving therapeutic efficacy at lower concentrations than previously required when administered alone.
2Reliability
If APIM-peptides are used as single active agents, then they show unclear effectiveness, but combining them with cytotoxic agents increases complexity
Solution Approach 1:
The modified APIM-peptide with integrated cell-penetrating capability serves its own delivery function, eliminating the need for complex combination regimens with cytotoxic agents. The peptide autonomously enters cells and persists intracellularly, demonstrating effectiveness as a single agent without requiring additional delivery systems or combination therapies.
3Productivity
If higher concentrations of APIM-peptides are administered, then cellular uptake is enhanced, but side effects in healthy cells increase
Solution Approach 1:
The patent changes the molecular parameters of the APIM-peptide by integrating a cell-penetrating peptide sequence, which fundamentally alters its cellular interaction properties. This modification enables efficient cellular uptake at lower concentrations and enhances selective persistence in cancer cells, reducing side effects in healthy cells compared to high-concentration administration of unmodified peptides.
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 peptide effectively treats carcinomas and sarcomas in humans at lower concentrations, demonstrating significant therapeutic efficacy and persistence within cells for days, reducing tumor size and preventing spread.
Implementation Method 1
The peptide comprises an amino acid sequence as set forth in SEQ ID NO: 1 and a cell penetrating peptide
Implementation Method 2
APIM-peptides are a group of peptides that interact with PCNA (proliferating cell nuclear antigen) via a novel PCNA interacting motif
Data Source
AI summary
The present invention relates to pharmaceutical compositions and methods for the treatment of carcinomas and sarcomas. In particular, the invention provides a pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt thereof for use in treating a carcinoma or a sarcoma in a human subject, wherein the peptide comprises an amino acid sequence as set forth in SEQ ID NO: 1 and a cell penetrating peptide and wherein the pharmaceutical composition is systemically administered to the subject weekly to provide a dose of the peptide of about 15-65 mg/m2 body surface area (BSA) per week, calculated as the free form of the peptide.