STRO-1 Antibody Variable Region for Stromal Cell Ablation
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Solution Overview
Problem
Current methods for stem cell transplants face challenges in achieving adequate engraftment due to the presence of resident stromal cells, which are not effectively ablated by pretransplant conditioning, hindering donor stromal cell engraftment and potentially requiring the inactivation of abnormal or virally altered resident stromal cells.
Innovation Solution
Development of recombinant STRO-1 antibodies that bind specifically to the STRO-1 cell surface protein, allowing for the isolation and inactivation of STRO-1 positive stem cells through conjugation with therapeutic agents such as radionuclides or chemotherapeutic agents, facilitating the engraftment of donor stromal cells and addressing abnormal resident stromal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pretransplant conditioning is used to prepare for stem cell transplant, then the transplant process can proceed, but resident stromal cells are not effectively ablated, hindering donor stromal cell engraftment
Solution Approach 1:
The patent extracts and removes the harmful resident stromal cells from the bone marrow niche before donor cell transplantation. This is achieved by administering anti-STRO-1 antibodies that specifically bind to and eliminate resident stromal cells, thereby clearing the niche for successful donor engraftment without requiring intensive conditioning that damages host tissue
Solution Approach 2:
The patent performs preliminary ablation of resident stromal cells using anti-STRO-1 antibodies before donor stem cell transplantation. This preliminary action prepares the bone marrow niche by removing competing resident cells, creating space and resources for donor cell engraftment while avoiding the need for harsh conditioning regimens
2Measurement precision
If conventional antibodies are used for cell isolation, then cells can be targeted, but the antibody sequences are not optimized for recombinant production and binding affinity
Solution Approach 1:
The patent optimizes the antibody variable region sequences by modifying specific amino acid parameters to enhance binding affinity to STRO-1. The optimized sequences (SEQ ID NOS: 1 and 2) incorporate specific mutations in the complementarity-determining regions that improve antigen binding while maintaining compatibility with recombinant expression systems
Solution Approach 2:
The patent creates optimized copies of the original anti-STRO-1 antibody variable regions. These recombinant antibody sequences are designed copies that retain the specific binding capability to STRO-1 while being engineered for improved expression in recombinant systems and enhanced binding affinity through rational sequence modifications
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
The use of STRO-1 antibodies enables the selective isolation and inactivation of STRO-1 positive cells, improving stem cell transplant outcomes by creating space for donor engraftment and allowing for the treatment of abnormal resident stromal cells, thereby enhancing the efficacy of stem cell therapies.
Implementation Method 1
the antibody binds to human STRO-1 cell surface protein
Data Source
AI summary
The amino acid sequence of the heavy chain polypeptide and the light chain polypeptide of the STRO-1 antibody is disclosed. Also disclosed are methods for detecting and isolating cells expressing the STRO-1 cell surface protein.