(211)Astatine-Conjugated Monoclonal CD45 Antibody-Based Nonmyeloablative Conditioning for Stem Cell Gene Therapy

Hum Gene Ther. 2015 Jun;26(6):399-406. doi: 10.1089/hum.2015.021.


Most hematopoietic stem cell gene therapy studies require host conditioning to allow for efficient engraftment of gene-modified cells. Conditioning regimens with lower treatment-related toxicities are especially relevant for the treatment of nonmalignant blood disorders, such as hemoglobinopathies and immunodeficiencies, and for patients who are otherwise ineligible for conventional high-dose conditioning. Radioimmunotherapy, which employs an α- or a β-emitting radionuclide conjugated to a targeting antibody, is effective for delivering cytotoxic doses of radiation to a cell type of interest while minimizing off-target toxicity. Here, we demonstrate the feasibility of using a nonmyeloablative dose of a monoclonal anti-CD45 antibody conjugated to the α-emitter Astatine-211 ((211)At) to promote engraftment of an autologous gene-modified stem cell graft in the canine model. The doses used provided myelosuppression with rapid autologous recovery and minimal off-target toxicity. Engraftment levels were low in all dogs and reflected the low numbers of gene-modified cells infused. Our data suggest that a cell dose exceeding 1×10(6) cells/kg be used with nonmyeloablative doses of (211)At-anti-CD45 monoclonal antibodies for sustained engraftment in the dog model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / toxicity
  • Astatine / chemistry*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dogs
  • Genetic Therapy / methods*
  • Hematopoietic Stem Cell Transplantation
  • Leukocyte Common Antigens / immunology*
  • Transgenes
  • Transplantation Conditioning / methods*
  • Tumor Suppressor Proteins / genetics


  • Antibodies, Monoclonal
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Leukocyte Common Antigens
  • DNA Repair Enzymes
  • Astatine