Details

Autor(en) / Beteiligte

• Green, Damian J.
• Shadman, Mazyar
• Jones, Jon C.
• Frayo, Shani L.
• Kenoyer, Aimee L.
• Hylarides, Mark D.
• Hamlin, Donald K.
• Wilbur, D. Scott
• Balkan, Ethan R.
• Lin, Yukang
• Miller, Brian W.
• Frost, Sofia.H.L.
• Gopal, Ajay K.
• Orozco, Johnnie J.
• Gooley, Theodore A.
• Laird, Kelly L.
• Till, Brian G.
• Bäck, Tom
• Sandmaier, Brenda M.
• Pagel, John M.
• Press, Oliver W.

Titel

Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

Ist Teil von

• Blood, 2015-03, Vol.125 (13), p.2111-2119

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• α-Emitting radionuclides deposit a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, 211At-labeled 1F5 monoclonal antibody (mAb) (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treated with doses of up to 48 µCi of 211At-labeled anti-CD20 mAb ([211At]1F5-B10) experienced modest responses (0% cures but two- to threefold prolongation of survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 µCi of [211At]1F5-B10. These findings suggest that α-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail. •α-Emitting radionuclides have the potential to overcome treatment-resistant lymphoma cell clones that evade other forms of therapy.•211At-labeled anti-CD20 monoclonal antibody eradicates lymphoma in a mouse minimal residual disease model.