Stem Cell Bispecific Antibody Delivery
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Solution Overview
Problem
Current recombinant bispecific antibodies (bsabs) used for retargeting effector T lymphocytes towards cancer cells have a short half-life, requiring continuous administration via external medical pump devices, which can be a source of infection, and there is a need for an alternative method to achieve sustained production and delivery of therapeutic antibodies.
Innovation Solution
Genetically modified pluri- or multipotent stem cells, such as human mesenchymal stem cells, engineered to express multispecific antibodies and a human immune cell co-stimulatory ligand, which continuously produce and secrete these antibodies in the body, providing an in situ delivery method for therapeutic antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant bispecific antibodies are continuously administered via external medical pump devices, then therapeutic effect is maintained, but infection risk increases and device complexity increases
Solution Approach 1:
The patent applies self-service by engineering patient's own stem cells to autonomously produce and secrete bispecific antibodies in vivo. The genetically modified stem cells function as self-sustaining therapeutic factories, eliminating the need for external pump devices and continuous external administration, thereby removing the infection risk associated with external devices while maintaining reliable therapeutic effects
Solution Approach 2:
The patent uses genetically modified stem cells as an intermediary between the patient's body and the therapeutic antibody. Instead of directly administering antibodies through external devices, the stem cells serve as a biological intermediary that produces and secretes the therapeutic antibody internally, bridging the gap between external therapy and internal physiological processes
2Reliability
If recombinant bispecific antibodies are continuously administered via external medical pump devices, then therapeutic effect is maintained, but device complexity and administration burden increase
Solution Approach 1:
The patent transforms the therapeutic system into a self-service model where genetically modified stem cells autonomously produce and secrete bisspecific antibodies continuously in vivo. This eliminates external pump devices and complex administration infrastructure, replacing them with a self-sustaining biological system that maintains reliable therapeutic effects without external intervention
Solution Approach 2:
The patent replaces the mechanical external pump device system with a biological production system. Instead of using mechanical devices to deliver antibodies, the body's own stem cells are engineered to function as biological factories, substituting mechanical delivery infrastructure with physiological production capabilities
3Reliability
If bispecific antibodies are administered continuously over prolonged time spans, then clinical response is achieved, but treatment duration and administration frequency increase
Solution Approach 1:
The patent applies preliminary action by genetically modifying stem cells before transplantation to establish long-term antibody production capability. The stem cells are pre-engineered with the genetic machinery to produce bisspecific antibodies, so that after transplantation they immediately begin sustained production without requiring repeated external administrations over prolonged time spans
Solution Approach 2:
The patent achieves continuity of useful action through the engineered stem cells that continuously produce and secrete bisspecific antibodies throughout their lifespan in the patient's body. This provides uninterrupted therapeutic action without the need for periodic external administrations, maintaining clinical response over the long term with a single transplantation event
Data Source
AI summary
The invention concerns pluri- or multipotent stem cells (SCs), e.g. human pluri- or multipotent stem cells (hSCs) engineered to express a multispecific antibody and which further express, on their surface, a human immune cell co-stimulatory ligand or an active fragment thereof.