Cell-Penetrating Peptide Antibody Conjugates for Intracellular Targeting
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Solution Overview
Problem
Current antibody therapeutics for cancer are limited in targeting intracellular cancer markers like PRL-1 and PRL-3 due to their inability to cross cell membranes, making it challenging to inhibit intracellular antigens and prevent cancer metastasis effectively.
Innovation Solution
Development of anti-PRL-1 and anti-PRL-3 monoclonal antibodies that can bind to intracellular targets, specifically designed to inhibit protein tyrosine phosphatase activity, allowing for the treatment and prevention of cancer metastasis by crossing the plasma membrane and targeting PRL-1 and PRL-3 expressing cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used for cancer therapy, then they can effectively target surface antigens, but they cannot cross the plasma membrane to reach intracellular targets
Solution Approach 1:
The patent employs cell-penetrating peptides (CPPs) as intermediary carriers that facilitate the transport of antibodies across the plasma membrane. The CPP-antibody conjugate system allows the antibody to reach intracellular targets while the CPP acts as a mediator that enables membrane traversal, thus resolving the contradiction between maintaining antibody specificity and achieving intracellular access.
Solution Approach 2:
The invention creates a composite therapeutic agent by chemically conjugating cell-penetrating peptides with antibodies. This composite structure combines the membrane-crossing capability of CPPs with the antigen-specific binding properties of antibodies, enabling the single molecule to perform both functions that were previously mutually exclusive.
2Reliability
If antibodies are modified to cross cell membranes, then they can reach intracellular targets, but their large size may prevent effective membrane crossing
Solution Approach 1:
The patent segments the therapeutic function into two distinct components: the cell-penetrating peptide handles membrane crossing, while the antibody handles antigen recognition and binding. This functional segmentation allows each component to optimize its specific role, with the small CPP navigating the membrane barrier and the large antibody performing its binding function once inside the cell.
Solution Approach 2:
The cell-penetrating peptide serves as an intermediary carrier that temporarily facilitates the antibody's passage through the membrane. The CPP's small size and membrane-crossing properties enable it to lead the way, allowing the larger antibody to follow through the membrane barrier that would otherwise be impassable.
3Reliability
If conventional antibody therapies are used, then they can treat surface-expressed antigens, but they cannot effectively prevent cancer metastasis by targeting intracellular PRL-1 and PRL-3
Solution Approach 1:
The patent creates a composite CPP-antibody conjugate specifically designed to target intracellular PRL-1 and PRL-3 proteins. The CPP component enables intracellular delivery while the antibody component provides specific recognition of PRL-1/PRL-3, allowing the therapy to address metastasis by targeting these intracellular markers that were previously inaccessible.
Solution Approach 2:
The cell-penetrating peptide acts as an intermediary delivery vehicle that transports the anti-PRL-1/PRL-3 antibodies into the cytoplasm where these proteins are located. This intermediary system enables the antibody to reach its intracellular target, facilitating metastasis prevention by blocking PRL-mediated signaling pathways.
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 antibodies significantly reduce metastatic tumor formation by at least 50% and can be used to treat various cancers such as colorectal, ovarian, and breast cancer by effectively binding to intracellular PRL-1 and PRL-3, offering a novel approach to addressing the challenge of intracellular antigen targeting.
Implementation Method 1
Antibodies are capable of recognising and binding to their antigens in a specific manner
Data Source
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AI summary
We provide an antibody capable of binding to an intracellular PRL-1 or PRL-3 polypeptide, in which the antibody is capable of binding to an epitope bound by an antibody 269, antibody 223 or antibody 318. Such anti-PRL antibodies may be capable of binding to intracellular PRL-1 or PRL-3. They may be suitable for use as therapies against cancer or metastasis thereof, or in clinical diagnosis to identify PRL-3 or PRL-1 positive patients.