Compositions and methods of immunodepletion for the treatment of malignant and non-malignant hematological diseases

A method for targeted depletion of a subject's hematopoietic stem cells, the method comprising:

• administering to the subject an effective amount of a conjugation of a radiolabeled antibody against CD135 and a bifunctional chelating agent,
• wherein the bifunctional chelating agent is p-SCN-Bn-DOTA,
• wherein the radiolabeled antibody comprises a radiolabel selected from 90Y, 177Lu, 186Re, 188Re, 153Sm, 225Ac, 212Bi, 213Bi, 227Th, 149Tb, and 212Pb,
• wherein the subject is afflicted with a non-cancerous disorder treatable via genetically edited cell therapy and is about to undergo such therapy to treat the non-cancerous disorder, and the effective amount of the radiolabeled antibody is administered as a single dose, and
• wherein the non-cancerous disorder is selected from the group consisting of sickle cell disease (SCD), severe combined immunodeficiency disease (SCID), and β-thalassemia.

A method for treating a subject afflicted with a cancerous disorder treatable via bone marrow transplant, the method comprising:

• (i) administering to the subject an amount of a radiolabeled antibody effective to deplete or ablate the subject's hematopoietic stem cells;
• and
• (ii) after a suitable time period, performing the bone marrow transplant on the subject to treat the subject's disorder,
• wherein the cancerous disorder is a leukemia or a lymphoma and the antibody comprises a conjugate of an anti-CD135 monoclonal antibody and a bifunctional chelating agent, wherein the bifunctional chelating agent is p-SCN-Bn-DOTA,
• wherein the radiolabeled antibody is labeled with 90Y, 177Lu, 186Re, 188Re, 153Sm, 225Ac, 212Bi, 213Bi, 227Th, 149Tb, or 212Pb.

A method for targeted depletion of a subject's hematopoietic stem cells, the method comprising:

• administering to the subject an effective amount of a radiolabeled antibody comprising a conjugate of an anti-CD135 monoclonal antibody and a bifunctional chelating agent,
• wherein the bifunctional chelating agent is p-SCN-Bn-DOTA,
• wherein the radiolabeled antibody comprises a radiolabel selected from 90Y, 177Lu, 186Re, 188Re, 153Sm, 225Ac, 212Bi, 213Bi, 227Th, 149Tb, and 212Pb and
• wherein the subject is afflicted with a CD135 (FLT-3) mutation in acute myeloid leukemia.