CD155-Targeting Antibody Blood-Brain Barrier Transcytosis
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Solution Overview
Problem
Current monoclonal antibodies face challenges in entering the central nervous system due to the restrictive nature of the blood-brain barrier, limiting their therapeutic effectiveness for brain tumors and neurological disorders.
Innovation Solution
Development of a monoclonal antibody targeting CD155 that can cross the blood-brain barrier, either by systemic administration or through other routes, allowing for the delivery of therapeutic agents such as mRNA or genes directly to the central nervous system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are administered systemically to treat brain tumors and neurological disorders, then therapeutic coverage is improved, but the blood-brain barrier prevents the antibodies from entering the central nervous system
Solution Approach 1:
The patent uses the CD155 receptor as an intermediary to facilitate antibody entry into the CNS. The monoclonal antibody is engineered to bind specifically to CD155, which is expressed on the surface of brain endothelial cells and tumor cells. This binding interaction mediates the transcytosis of the antibody across the blood-brain barrier, enabling therapeutic delivery to the CNS without direct penetration through the barrier's tight junctions.
Solution Approach 2:
The patent modifies the parameters of the monoclonal antibody by engineering specific binding affinity to the CD155 receptor. This parameter change in binding specificity enables the antibody to be recognized and transported by CD155-expressing cells, transforming it from a molecule that cannot cross the BBB into one that can actively enter the CNS through receptor-mediated transcytosis.
2Ease of operation
If the blood-brain barrier is made more permeable to allow antibody entry, then therapeutic delivery is improved, but the barrier's protective function against toxins and pathogens is compromised
Solution Approach 1:
The CD155 receptor serves as a selective intermediary that mediates antibody transport without compromising the overall integrity of the blood-brain barrier. The receptor is naturally expressed on brain endothelial cells and provides a specific pathway for CD155-binding antibodies, while the barrier's tight junctions remain intact to block non-specific passage of toxins and pathogens. This selective mediation allows therapeutic delivery without general barrier disruption.
Solution Approach 2:
The patent exploits the local quality of CD155 expression on specific cell surfaces (brain endothelial cells and tumor cells) to enable targeted antibody entry. The antibody binds locally to CD155 at the blood-brain barrier interface and is selectively transported through transcytosis, while the rest of the barrier maintains its protective function. This localized interaction allows permeability enhancement only where needed, without compromising overall barrier integrity.
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
Enables the treatment of neurological disorders and brain tumors by facilitating the entry of therapeutic agents into the brain, overcoming the barrier that previously prevented monoclonal antibodies from reaching their target in the central nervous system.
Implementation Method 1
a non-viral ligand capable of binding to CD155... wherein the ligand is conjugated to the therapeutic agent
Data Source
AI summary
A humanized antibody to the poliovirus receptor can be used to target nucleic acids, proteins, and chemicals to brain cancer cells, thus providing treatment for tumors that are otherwise hard to treat due to the difficulty of getting treatments through the blood brain barrier.