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
Life of this patent
Estimating the term…
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.
Claims49
A method of conditioning a human subject having a hemoglobinopathy for hematopoietic stem cell transplantation, the method comprising administering to a human subject an amount of an immunotoxin effective to condition the human subject for hematopoietic stem cell engraftment by selectively depleting endogenous hematopoietic stem cells in the human subject,
- wherein the immunotoxin comprises an antibody, or an antigen-binding fragment thereof, conjugated to a toxin, wherein the immunotoxin selectively binds to the endogenous hematopoietic stem cells, wherein the immunotoxin is internalized by the endogenous hematopoietic stem cells, wherein the immunotoxin is capable of conditioning an immunocompetent subject, and wherein the method does not induce life-threatening anemia in the human subject prior to transplantation of hematopoietic stem cells.
A method of conditioning a human subject for hematopoietic stem cell transplantation, the method comprising administering to the human subject an amount of an immunotoxin effective to condition bone marrow in the human subject for hematopoietic stem cell engraftment by selectively depleting endogenous hematopoietic stem cells in the bone marrow of the human subject,
- wherein the immunotoxin comprises an antibody, or an antigen-binding fragment thereof, coupled to a toxin, wherein the antibody, or the antigen-binding fragment thereof, selectively binds to human CD117;
- wherein the immunotoxin is internalized by the endogenous hematopoietic stem cells;
- wherein the immunotoxin is capable of conditioning an immunocompetent subject;
- and
- wherein the method does not induce life-threatening anemia in the human subject prior to transplantation of hematopoietic stem cells.
A method of a hematopoietic stem cell transplantation in a human subject, the method comprising
- administering to a human subject an amount of an immunotoxin effective to condition the human subject for hematopoietic stem cell engraftment by selectively depleting endogenous hematopoietic stem cells in the human subject, and
- administering a transplant comprising hematopoietic stem cells to the human subject,
- wherein the immunotoxin comprises an antibody, or an antigen-binding fragment thereof, conjugated to a toxin, wherein the immunotoxin selectively binds to a human CD45 cell surface protein, wherein the immunotoxin is internalized by the endogenous hematopoietic stem cells, wherein the immunotoxin is capable of conditioning an immunocompetent subject.
Dependencies are inferred from the claim text.