CD117 Antibodies for Selective Stem Cell Depletion
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Solution Overview
Problem
There is a need for effective compositions and methods to target specific endogenous stem cells for promoting the engraftment of exogenous hematopoietic stem cell grafts during transplantation, while preserving the multi-potency and hematopoietic functionality of these cells, as existing therapies face challenges in ensuring successful engraftment and treating hematopoietic system-related diseases.
Innovation Solution
Development of antibodies and antigen-binding fragments that specifically bind to human CD117, used in antibody drug conjugates (ADCs), which can deplete populations of CD117+ cells, creating a niche for transplanted hematopoietic stem cells by administering these antibodies or fragments conjugated to cytotoxins before or during transplantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD117-targeted therapy is used to deplete endogenous hematopoietic stem cells, then engraftment of exogenous grafts is promoted, but multi-potency and hematopoietic functionality of remaining cells may be compromised
Solution Approach 1:
The patent applies local quality by differentiating between aberrant CD117+ cells (target for depletion) and normal hematopoietic stem cells (to be preserved). The antibody therapy is designed to selectively target and deplete only the aberrant cells while sparring normal cells, thereby maintaining multi-potency and hematopoietic functionality while achieving engraftment promotion.
2Reliability
If CD117+ cells are depleted to create niche for transplanted cells, then engraftment is enhanced, but loss of normal hematopoietic function occurs
Solution Approach 1:
The patent converts the harmful effect of CD117 expression (which normally supports hematopoietic function) into a beneficial target for selective depletion of aberrant cells. By targeting CD117 on aberrant cells rather than all CD117+ cells, the therapy eliminates the harmful presence of malignant or autoimmune cells while preserving the beneficial hematopoietic function of normal stem cells.
3Object-affected harmful factors
If existing CD117-targeted therapies are used, then cancer treatment is achieved, but engraftment promotion is insufficient
Solution Approach 1:
The patent applies universality by designing a CD117-targeted therapy that performs multiple functions: (1) eliminating aberrant CD117+ cells (cancer or autoimmune cells), and (2) promoting engraftment of exogenous hematopoietic stem cell grafts. This multi-functional approach addresses both cancer treatment and transplantation success, which were previously addressed by separate therapies.
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 approach effectively depletes aberrant CD117+ cells, such as cancer or autoimmune cells, and endogenous hematopoietic stem cells, allowing for the successful engraftment and functionality of transplanted cells, treating various hematopoietic disorders, cancers, and autoimmune diseases by creating a suitable environment for the transplanted cells to populate and restore deficient cell types.
Implementation Method 1
administering an antibody or antigen-binding fragment thereof, or an ADC, capable of binding CD117
Data Source
AI summary
The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.