Compositions and methods for non-myeloablative conditioning
AssigneesPresident and Fellows of Harvard College, The General Hospital Corporation, Children's Medical Center Corporation
InventorsDavid T. Scadden, Rahul Palchaudhuri, Derrick J. Rossi, Agnieszka D. Czechowicz
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Abstract
Disclosed herein are non-myeloablative antibody-toxin conjugates and compositions that target cell surface markers, such as the CD34, CD45 or CD117 receptors, and related methods of their use to effectively conditioning a subject's tissues (e.g., bone marrow tissue) prior to engraftment or transplant. The compositions and methods disclosed herein may be used to condition a subject's tissues in advance of, for example, hematopoietic stem cell transplant and advantageously such compositions and methods do not cause the toxicities that are commonly associated with traditional conditioning methods.
Claims12
A method of conditioning a subject for engraftment, the method comprising selectively depleting or ablating an endogenous hematopoietic stem cell (HSC) or progenitor cell population in a target tissue of an immunocompetent subject comprising administering to the subject an effective amount of an antibody coupled to a toxin,
- wherein:
- the antibody binds to CD117;
- the method does not induce anemia in the subject;
- and
- the toxin is internalized by an endogenous HSC or progenitor cell population, thereby depleting or ablating the endogenous hematopoietic stem cell or progenitor cell population in the target tissue.
A method of conditioning a subject for engraftment, the method comprising selectively depleting or ablating an endogenous hematopoietic stem cell (HSC) or progenitor cell population in a target tissue of an immunocompetent subject comprising administering to the subject an effective amount of an antibody coupled to a toxin,
- wherein:
- the antibody comprises a complementarity determining region that is the same as the complementarity determining region for one or more antibodies selected from clone A3C6E2 and clone 2B8;
- the toxin is an amatoxin;
- the method does not induce anemia in the subject;
- and
- the toxin is internalized by an endogenous HSC or progenitor cell population, thereby depleting or ablating the endogenous hematopoietic stem cell or progenitor cell population in the target tissue.
Dependencies are inferred from the claim text.