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024 7 _ |a 10.1016/j.canlet.2016.08.007
|2 doi
024 7 _ |a pmid:27524505
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024 7 _ |a 0304-3835
|2 ISSN
024 7 _ |a 1872-7980
|2 ISSN
024 7 _ |a altmetric:17890332
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037 _ _ |a DKFZ-2018-00485
041 _ _ |a eng
082 _ _ |a 570
100 1 _ |a Weber, Tobias
|b 0
245 _ _ |a Preclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.
260 _ _ |a Amsterdam [u.a.]
|c 2016
|b Elsevier Science
336 7 _ |a article
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520 _ _ |a Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL.
536 _ _ |a 315 - Imaging and radiooncology (POF3-315)
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Antibodies, Bispecific
|2 NLM Chemicals
650 _ 7 |a Antibodies, Monoclonal, Humanized
|2 NLM Chemicals
650 _ 7 |a CD22 protein, human
|2 NLM Chemicals
650 _ 7 |a Forkhead Transcription Factors
|2 NLM Chemicals
650 _ 7 |a Homeodomain Proteins
|2 NLM Chemicals
650 _ 7 |a Il2rg protein, mouse
|2 NLM Chemicals
650 _ 7 |a Immunoconjugates
|2 NLM Chemicals
650 _ 7 |a Immunoglobulins, Intravenous
|2 NLM Chemicals
650 _ 7 |a Interleukin Receptor Common gamma Subunit
|2 NLM Chemicals
650 _ 7 |a Radioisotopes
|2 NLM Chemicals
650 _ 7 |a Sialic Acid Binding Ig-like Lectin 2
|2 NLM Chemicals
650 _ 7 |a Whn protein
|2 NLM Chemicals
650 _ 7 |a RAG-1 protein
|0 128559-51-3
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650 _ 7 |a Rituximab
|0 4F4X42SYQ6
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650 _ 7 |a Lutetium
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700 1 _ |a Bötticher, Benedikt
|b 1
700 1 _ |a Arndt, Michaela
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700 1 _ |a Mier, Walter
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700 1 _ |a Sauter, Max Benedikt
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700 1 _ |a Exner, Evelyn
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700 1 _ |a Keller, Armin
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700 1 _ |a Krämer, Susanne
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700 1 _ |a Leotta, Karin
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700 1 _ |a Wischnjow, Artjom
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700 1 _ |a Grosse-Hovest, Ludger
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700 1 _ |a Strumberg, Dirk
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700 1 _ |a Jäger, Dirk
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700 1 _ |a Gröne, Hermann-Josef
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700 1 _ |a Haberkorn, Uwe
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700 1 _ |a Brem, Gottfried
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700 1 _ |a Krauss, Jürgen
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773 _ _ |a 10.1016/j.canlet.2016.08.007
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