Non-cytotoxic Modified Cells for Targeted Signaling Modulation
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Solution Overview
Problem
Current methods for delivering therapeutic antibodies and ligands to specific cells or tissues face challenges such as difficulty in crossing the blood-brain barrier, short half-life, high immunogenicity, and inability to target specific cell types effectively.
Innovation Solution
The use of modified cells expressing a chimeric transmembrane polypeptide with an extracellular target receptor-binding domain, a transmembrane domain, and an intracellular domain that does not transduce a signal, allowing for targeted modulation of signaling by a target receptor in a target cell.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic antibodies and ligands are used to target specific cells or tissues, then the treatment can address the disease mechanism, but the molecules face difficulty in crossing the blood-brain barrier, have short half-life, high immunogenicity, and cannot target specific cell types effectively
Solution Approach 1:
The patent uses modified cells as intermediary carriers to deliver therapeutic molecules to target cells. These modified cells express chimeric transmembrane polypeptides that enable them to home to specific tissues and deliver the therapeutic payload, thereby overcoming the limitations of direct molecule administration including short half-life and poor tissue penetration
Solution Approach 2:
The patent modifies the parameters of the delivery system by engineering cells to express specific chimeric transmembrane polypeptides with tailored properties. This includes modifying cell surface characteristics, homing capabilities, and therapeutic molecule presentation, thereby improving targeting effectiveness and extending functional duration in vivo
2Reliability
If cells are used to deliver therapeutic molecules, then the delivery can overcome blood-brain barrier and tissue penetration issues, but the cells may activate the immune system causing localized inflammation or direct killing of the treated cells
Solution Approach 1:
The patent converts the potential harmful immune recognition of modified cells into a beneficial feature by designing chimeric transmembrane polypeptides that can modulate immune cell activity. The intracellular domain is specifically designed to prevent activation of the immune cell itself while allowing modulation of target cell signaling, thereby turning potential cytotoxicity into a protective mechanism
Solution Approach 2:
The patent applies local quality by designing the chimeric transmembrane polypeptide with distinct functional domains: the extracellular domain for target recognition and binding, the transmembrane domain for anchoring, and a specially designed intracellular domain that does not transduce activation signals. This localized functional differentiation allows the cell to deliver therapy without triggering harmful immune responses
3Ease of manufacture
If conventional delivery methods are used, then the process is simpler, but the therapeutic molecules cannot reach the intended target region or induce appropriate cellular response
Solution Approach 1:
The patent introduces modified cells as intermediary delivery vehicles that can navigate to target tissues and deliver therapeutic molecules effectively. This intermediary approach balances the simplicity of cell-based delivery with the reliability of targeted therapy, overcoming the limitations of both direct molecule administration and complex viral delivery systems
Data Source
AI summary
Modified cells comprising a transmembrane polypeptide comprising at least one extracellular target receptor-binding domain, a transmembrane domain and an intracellular domain, wherein said intracellular domain is not capable of transducing any signal are provided. Methods of inducing or inhibiting signaling by a target receptor in a target cell comprising contacting the target cell with a modified cell of the invention are also provided.