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000132842 0247_ $$2doi$$a10.1016/j.canlet.2016.08.007
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000132842 0247_ $$2ISSN$$a0304-3835
000132842 0247_ $$2ISSN$$a1872-7980
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000132842 037__ $$aDKFZ-2018-00485
000132842 041__ $$aeng
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000132842 1001_ $$aWeber, Tobias$$b0
000132842 245__ $$aPreclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.
000132842 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2016
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000132842 520__ $$aRadioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL.
000132842 536__ $$0G:(DE-HGF)POF3-315$$a315 - Imaging and radiooncology (POF3-315)$$cPOF3-315$$fPOF III$$x0
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000132842 650_7 $$2NLM Chemicals$$aAntibodies, Bispecific
000132842 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal, Humanized
000132842 650_7 $$2NLM Chemicals$$aCD22 protein, human
000132842 650_7 $$2NLM Chemicals$$aForkhead Transcription Factors
000132842 650_7 $$2NLM Chemicals$$aHomeodomain Proteins
000132842 650_7 $$2NLM Chemicals$$aIl2rg protein, mouse
000132842 650_7 $$2NLM Chemicals$$aImmunoconjugates
000132842 650_7 $$2NLM Chemicals$$aImmunoglobulins, Intravenous
000132842 650_7 $$2NLM Chemicals$$aInterleukin Receptor Common gamma Subunit
000132842 650_7 $$2NLM Chemicals$$aRadioisotopes
000132842 650_7 $$2NLM Chemicals$$aSialic Acid Binding Ig-like Lectin 2
000132842 650_7 $$2NLM Chemicals$$aWhn protein
000132842 650_7 $$0128559-51-3$$2NLM Chemicals$$aRAG-1 protein
000132842 650_7 $$04F4X42SYQ6$$2NLM Chemicals$$aRituximab
000132842 650_7 $$05H0DOZ21UJ$$2NLM Chemicals$$aLutetium
000132842 7001_ $$aBötticher, Benedikt$$b1
000132842 7001_ $$0P:(DE-He78)25866e5f0faaf24f74afbfa0b1708129$$aArndt, Michaela$$b2$$udkfz
000132842 7001_ $$aMier, Walter$$b3
000132842 7001_ $$0P:(DE-He78)a27964412d8159e07c55f8105401cb0f$$aSauter, Max Benedikt$$b4$$udkfz
000132842 7001_ $$aExner, Evelyn$$b5
000132842 7001_ $$aKeller, Armin$$b6
000132842 7001_ $$aKrämer, Susanne$$b7
000132842 7001_ $$0P:(DE-He78)c1b2ff9645588258d53aea1ccce6ddcf$$aLeotta, Karin$$b8$$udkfz
000132842 7001_ $$aWischnjow, Artjom$$b9
000132842 7001_ $$aGrosse-Hovest, Ludger$$b10
000132842 7001_ $$aStrumberg, Dirk$$b11
000132842 7001_ $$0P:(DE-He78)ed0321409c9cde20b380ae663dbcefd1$$aJäger, Dirk$$b12$$udkfz
000132842 7001_ $$0P:(DE-He78)00a2ea610aee4a8fca32908fc3d02e91$$aGröne, Hermann-Josef$$b13$$udkfz
000132842 7001_ $$0P:(DE-He78)13a0afba029f5f64dc18b25ef7499558$$aHaberkorn, Uwe$$b14$$udkfz
000132842 7001_ $$aBrem, Gottfried$$b15
000132842 7001_ $$aKrauss, Jürgen$$b16
000132842 773__ $$0PERI:(DE-600)2004212-7$$a10.1016/j.canlet.2016.08.007$$gVol. 381, no. 2, p. 296 - 304$$n2$$p296 - 304$$tCancer letters$$v381$$x0304-3835$$y2016
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