Modified B Cells for Bone Metastasis Targeting
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Solution Overview
Problem
Current treatments for cancer metastasis, particularly in bone, are refractory and do not effectively address the long-term management of chronic diseases like metastatic cancer.
Innovation Solution
Genetically modified autologous and/or allogenic differentiated B cell compositions, such as plasmablasts, plasma cells, or memory B cells, are modified ex vivo using transposon systems to express scFv that can bind tumor-associated antigens, allowing them to home to bone marrow and release therapeutic proteins directly at the cancer site.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional cancer treatments are used, then initial cancer control may be achieved, but long-term management of metastatic cancer remains refractory
Solution Approach 1:
The patent modifies B cells ex vivo before administration to express therapeutic antibodies and homing receptors in advance. This preliminary genetic modification ensures that when the cells are administered, they are pre-equipped to migrate to bone marrow and deliver therapeutic agents continuously, resolving the contradiction between initial control and long-term efficacy.
Solution Approach 2:
The modified B cells autonomously migrate to bone marrow using endogenous chemokine gradients and continuously produce therapeutic antibodies in vivo. This self-service mechanism eliminates the need for repeated administrations and maintains long-term therapeutic effect, addressing both duration and reliability concerns.
2Reliability
If therapeutic agents are administered systemically, then cancer cells may be reached, but lack of targeted delivery reduces efficacy
Solution Approach 1:
The patent uses modified B cells as intermediary carriers that express homing receptors (e.g., CXCR4) to navigate to bone marrow and deliver therapeutic antibodies locally. This intermediary approach achieves targeted delivery without requiring complex external guidance systems, balancing efficacy with ease of manufacture.
3Duration of action of moving object
If short-lived B cells are used, then rapid production is possible, but long-term expression of therapeutic agents cannot be sustained
Solution Approach 1:
The patent employs plasmablasts, which are dynamically positioned between short-lived activated B cells and long-lived plasma cells. Plasmablasts can rapidly proliferate and then differentiate into long-lived plasma cells that persist in bone marrow for months to years, thereby achieving both rapid initial production and sustained long-term expression.
Data Source
AI summary
The present disclosure provides genetically modified autologous and/or allogenic B cell compositions and methods for treatment of cancer and/or metastatic cancer. B cells are modified ex vivo. The genetically modified B cell express at least one therapeutic protein, wherein the modified B cell is CD38+, CD138+, CD78+, IL-6R+, and CD27++ and wherein the modified B cell is capable of homing to bone marrow for improved efficacy of cancer treatment. In typical embodiments, the therapeutic protein is capable of binding a tumor associated antigen (TAA) located within the bone-localized cancer. The administered modified B cell composition can express and release the therapeutic protein at the cancer site, typically within bone.