Compositions and methods for non-genotoxic conditioning
AssigneeMaro Bio Inc.
InventorsAkanksha Chhabra, Vanessa Soros, Alan Le
Life of this patent
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Abstract
Provided herein are methods and compositions relating to the use of anti-CD1 10 and anti-CD117 conditioning agents for depletion of endogenous hematopoietic stem cells in a subject, for example. prior to hematopoietic stem cell transplantation. Also provided are cell-based therapy methods and compositions.
Claims86
A method of hematopoietic stem cell engraftment in a subject in need thereof, the method comprising:
- a. depleting endogenous hematopoietic stem cells in the subject by administering to the subject a pharmaceutical composition comprising:
- i. a first targeting moiety that specifically binds CD117;
- and
- ii. a second targeting moiety that specifically binds CD110;
- and
- b. administering exogenous hematopoietic stem cells to the subject;
- wherein administration of the pharmaceutical composition mediates engraftment of the exogenous hematopoietic stem cells resulting in multi-lineage hematopoietic reconstitution in the subject.
A method of hematopoietic stem cell engraftment in a subject in need thereof, the method comprising:
- a. depleting endogenous hematopoietic stem cells in the subject by co-administering to the subject:
- i. an effective amount of a first isolated antibody, or an antigen-binding fragment thereof, that specifically binds CD117;
- and
- ii. an effective amount of a second isolated antibody, or an antigen-binding fragment thereof, that specifically binds CD110;
- and
- b. administering exogenous hematopoietic stem cells to the subject;
- wherein co-administration of the effective amounts of the first and second antibodies, or fragments thereof, synergistically mediates engraftment of the exogenous hematopoietic stem cells resulting in multi-lineage hematopoietic reconstitution in the subject.
The method of claim 134 wherein the CD34+ HSPCs comprise CD34+/CD38−/CD90+/CD45RA-HSPCs.
A method of depleting endogenous hematopoietic stem cells in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising:
- a. a first targeting moiety that specifically binds CD117;
- and
- b. a second targeting moiety that specifically binds CD110.
The method of claim 58, wherein administration of the pharmaceutical composition mediates depletion of the exogenous hematopoietic stem cells in the subject. 60 The method of claim 58 or 59, wherein the first and second moiety bind hematopoietic stem cells co-expressing CD117 and CD110.
A method of depleting endogenous hematopoietic stem cells in a subject in need thereof, the method comprising co-administering to the subject:
- a. an effective amount of a first isolated antibody, or an antigen-binding fragment thereof, that specifically binds CD117;
- and
- b. an effective amount of a second isolated antibody, or an antigen-binding fragment thereof, that specifically binds CD110.
Dependencies are inferred from the claim text.