Details

Autor(en) / Beteiligte

• Sharkey, Robert M.
• Karacay, Habibe
• Goldenberg, David M.

Titel

Improving the treatment of non‐Hodgkin lymphoma with antibody‐targeted radionuclides

Ist Teil von

• Cancer, 2010-02, Vol.116 (S4), p.1134-1145

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Radioimmunotherapy of non‐Hodgkin lymphoma comprises a 90Y‐ or 131I‐labeled murine anti‐CD20 IgG, but both agents also include a substantial dose of unlabeled anti‐CD20 IgG given immediately before the radioconjugate to reduce its uptake in the spleen (primary normal B‐cell antigen sink); this extends its plasma half‐life and improves tumor visualization. Thus, these treatments combine an effective anti‐CD20 radioconjugate with an unconjugated anti‐CD20 antibody that is also therapeutically active, but the large anti‐CD20 IgG predose (∼900 mg) may diminish the tumor localization of the radioimmunoconjugate (eg, 10‐35 mg). We have examined alternative approaches that enhance radionuclide targeting and improve antitumor responses. One uses a 90Y‐labeled anti‐CD22 IgG (epratuzumab) combined with an antibody therapy regimen of a humanized anti‐CD20 IgG (veltuzumab). Pretargeted radionuclide therapy using a trivalent, humanized, recombinant bispecific anti‐CD20 antibody with a 90Y‐hapten‐peptide is another highly effective method that is also less toxic than directly radiolabeled IgG. Finally, all approaches benefit from the addition of a consolidation‐dosing regimen of the anti‐CD20 IgG antibody. This article reviews these various options and discusses how some fundamental changes could potentially enhance the response and duration from radionuclide‐targeted therapy Cancer 2010;116(4 suppl):1134–45. © 2010 American Cancer Society. Radioimmunotherapy is a safe and effective treatment of non‐Hodgkin lymphoma that combines an anti‐CD20 IgG radioconjugate with a large amount of unlabeled anti‐CD20 antibody intended to allow the radioimmunoconjugate to bypass the CD20 antigen sink, but in excess, it could compromise the efficacy of the radioconjugate. Other approaches, such as combining anti‐CD20 antibody therapy with radioimmunoconjugate that binds to another B‐cell specific antigen, can enhance responses, or in the case of pretargeting procedures with consolidation anti‐CD20 antibody therapy, enhance responses with reduced toxicity.