Engineered B Cells Secreting Therapeutic Proteins
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Solution Overview
Problem
Current therapeutic protein treatments, such as antibody-based therapies for diseases like HIV, face challenges with transient protein presence in the body and limited persistence of engineered cells, leading to short-term therapeutic effects.
Innovation Solution
Engineered B cells are developed to express and secrete exogenous proteins, including antibodies, with modifications that enhance their production and persistence, such as conditional expression and prevention of class-switching, allowing for long-term therapeutic protein delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If repeated injections of recombinant therapeutic proteins are administered, then therapeutic effects are achieved, but the duration of action is limited and requires frequent treatment
Solution Approach 1:
The patent segments the therapeutic system into two components: (1) engineered B cells that serve as living factories, and (2) the therapeutic protein product they continuously secrete. This segmentation allows the therapeutic effect to be sustained through continuous production by the engineered cells rather than repeated external administration.
Solution Approach 2:
The engineered B cells are designed to autonomously and continuously secrete therapeutic proteins without requiring external stimulation or repeated injections. The cells self-maintain their protein production capability through integrated nucleic acid sequences that drive constitutive expression, effectively serving themselves as persistent therapeutic sources.
2Productivity
If engineered B cells are modified to enhance protein production, then therapeutic efficacy is improved, but cell persistence and stability may be compromised
Solution Approach 1:
The patent merges multiple functional elements into a single integrated nucleic acid construct that is introduced into the B cells. This construct combines: (1) strong constitutive promoters for continuous protein expression, (2) sequences encoding the therapeutic protein, and (3) elements that ensure stable integration and maintenance. The merging of these elements ensures coordinated function that maintains both high productivity and cell persistence.
Solution Approach 2:
The patent utilizes constitutive promoters that maintain high-level expression across varying cellular conditions and time. By changing the regulatory parameters from inducible or transient expression systems to constitutive promoters, the system achieves stable, long-term protein production without compromising cell survival or persistence in the host environment.
Data Source
AI summary
Provided herein are engineered B cells, such as for adoptive cell therapy. In some aspects, also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells are engineered to produce and/or secrete an exogenous protein, such as a therapeutic protein, including antibodies and antigen-binding fragments thereof. In some aspects, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence of the cells.