Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts.
Although radioimmunotherapy with radiolabeled intact monoclonal antibodies has demonstrated efficacy in the treatment of lymphoma, it provides low tumor-to-normal-tissue radionuclide target ratios and unwanted prolonged radiation exposure to the bone marrow. To overcome these obstacles, the administration of the radionuclide was separated from that of the antibody by using an anti-IL-2 receptor alpha antibody single chain Fv-streptavidin fusion protein, followed by radiolabeled biotin to treat lymphoma or leukemia xenografted mice. This Pretarget approach provided extremely rapid and effective tumor targeting, permitting the use of short-lived alpha-emitting radionuclides. With the beta-emitter (90)Y, all of the 10 lymphoma-xenografted mice were cured. With the alpha-emitter (213)Bi, significant efficacy was obtained in treating leukemic mice, and, furthermore, when combined with immunotherapy, 7 of 10 leukemic mice were cured. Thus, Pretarget radioimmunotherapy is very promising and could represent the next generation in the treatment of lymphoma and leukemia.
Zhang
Meili
M
Metabolism and Radiation Oncology Branches, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1374, USA.
Zhang
Zhuo
Z
Garmestani
Kayhan
K
Schultz
Jody
J
Axworthy
Donald B
DB
Goldman
Carolyn K
CK
Brechbiel
Martin W
MW
Carrasquillo
Jorge A
JA
Waldmann
Thomas A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D007938:Leukemia / Q000532:radiotherapy*; D008223:Lymphoma / Q000532:radiotherapy*; D051379:Mice; D016499:Radioimmunotherapy; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D019809:Streptavidin / Q000276:immunology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D019809:Streptavidin