Anti-CD45 Antibodies for Host Cell Depletion Before HSC Engraftment
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Solution Overview
Problem
Existing hematopoietic stem cell therapies face challenges in ensuring engraftment due to immunostimulatory and effector functions triggered by antibodies targeting cell surface antigens, hindering the successful transplantation of exogenous HSCs.
Innovation Solution
Development of anti-CD45 antibodies and antibody drug conjugates (ADCs) that specifically bind to CD45 on hematopoietic stem cells, allowing for targeted depletion of host cells and promoting the engraftment of exogenous grafts while preserving hematopoietic functionality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies target cell surface antigens on hematopoietic stem cells, then immunostimulatory and effector functions are triggered, but engraftment of exogenous HSCs is impeded
Solution Approach 1:
The patent extracts and eliminates the harmful immunostimulatory and effector functions associated with conventional antibody therapies while preserving the desired cell depletion effect. This is achieved by using anti-CD45 antibodies that specifically deplete host HSCs and immune cells without triggering the harmful immunostimulatory responses that prevent engraftment
Solution Approach 2:
The patent changes the target parameter from conventional cell surface antigens to CD45, a pan-hematopoietic cell marker. This parameter change allows for specific depletion of host cells while avoiding the immunostimulatory effects associated with targeting other antigens, thereby enabling successful engraftment
2Reliability
If anti-CD45 antibodies deplete host cells, then engraftment of exogenous HSCs is promoted, but unwanted immunostimulatory effects may occur
Solution Approach 1:
The patent applies preliminary depletion of host CD45+ cells before transplantation of exogenous HSCs. This preliminary action clears the way for engraftment while the specific timing and dosing regimens are designed to minimize immunostimulatory effects that could interfere with subsequent engraftment
3Productivity
If conventional antibody therapies are used, then cell surface antigens are targeted, but successful transplantation of exogenous HSCs is hindered
Solution Approach 1:
The patent uses CD45 as an intermediary target that is present on all hematopoietic cells. By targeting this universal marker rather than specific lineage markers, the therapy achieves comprehensive host cell depletion while avoiding the immunostimulatory effects associated with targeting specific cell types, thereby improving both transplantation success and engraftment efficiency
Data Source
AI summary
Disclosed are anti-CD45 antibodies, antigen binding fragments thereof, and antibody drug conjugates (ADCs) that specifically bind to human CD45. Such antibodies and ADCs are useful in therapeutic methods, including methods of depleting CD45+ cells from a patient. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD45+ 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 CD45+ cells prior to the transplant procedure.