Engineered Plasma Cells for Sustained BTCE Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for producing and delivering bispecific antibodies, such as BTCEs, face significant production challenges and require continuous high-dose infusions due to their short half-lives, posing difficulties for patients, especially those with limited hospital access.
Innovation Solution
A homology directed repair strategy is employed to generate engineered plasma cells (ePCs) that stably express BTCEs, leveraging their long lifespan and high secretory capacity for sustained therapeutic delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bispecific antibodies are administered to achieve therapeutic effect, then cancer cells can be targeted and killed, but continuous high-dose infusions are required due to short half-life
Solution Approach 1:
The patent introduces engineered plasma cells as an intermediary system that produces and secretes BTCEs in vivo. These engineered cells act as a living factory, continuously supplying the therapeutic agent without requiring repeated external administrations. The plasma cells are modified to express the BTCE gene and are designed to persist long-term in the patient's body, thereby extending the duration of therapeutic action.
Solution Approach 2:
The engineered plasma cells are designed to self-sustain their function by continuously producing and secreting BTCEs autonomously. Once introduced into the patient, these cells establish themselves and maintain therapeutic agent production without requiring external intervention or repeated infusions, effectively serving themselves as a permanent therapeutic delivery system.
2Reliability
If continuous high-dose infusions are administered, then therapeutic effect is maintained, but patient convenience and accessibility are reduced
Solution Approach 1:
The patent performs preliminary action by introducing engineered plasma cells that will continuously produce the therapeutic agent in advance. This single initial administration establishes a self-sustaining system that eliminates the need for subsequent repeated infusions, thereby dramatically improving patient convenience and accessibility while maintaining reliable therapeutic effect.
3Reliability
If high doses are administered frequently, then therapeutic efficacy is maintained, but on-target adverse effects increase
Solution Approach 1:
The engineered plasma cells provide periodic secretion of BTCEs at physiologically appropriate levels rather than continuous high-dose administration. This controlled, sustained release pattern maintains therapeutic efficacy while avoiding the peaks in drug concentration that cause on-target adverse effects, thereby improving the therapeutic index.
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
ePCs effectively promote T-cell driven killing of cancer cells, including cell lines and patient-derived B-ALL xenografts, offering a stable and localized delivery of BTCEs, potentially reducing on-target adverse effects and eliminating the need for frequent infusions.
Implementation Method 1
a first polynucleotide encoding a homology direct repair (HDR) template comprising the expression cassette
Implementation Method 2
The CRISPR/Cas9 system has emerged as a powerful tool for genome editing, including the insertion of transgenes at specific genomic loci
Data Source
AI summary
Some embodiments of the method and compositions provided herein relate to methods of preparing cells expressing bispecific T cell engagers (BTCEs), and the use of such cells in certain therapies. In some embodiments, the cells are B cells or B cell precursors.