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@ARTICLE{Weber:132842,
      author       = {T. Weber and B. Bötticher and M. Arndt$^*$ and W. Mier and
                      M. B. Sauter$^*$ and E. Exner and A. Keller and S. Krämer
                      and K. Leotta$^*$ and A. Wischnjow and L. Grosse-Hovest and
                      D. Strumberg and D. Jäger$^*$ and H.-J. Gröne$^*$ and U.
                      Haberkorn$^*$ and G. Brem and J. Krauss},
      title        = {{P}reclinical evaluation of a diabody-based
                      (177){L}u-radioimmunoconjugate for {CD}22-directed
                      radioimmunotherapy in a non-{H}odgkin lymphoma mouse model.},
      journal      = {Cancer letters},
      volume       = {381},
      number       = {2},
      issn         = {0304-3835},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2018-00485},
      pages        = {296 - 304},
      year         = {2016},
      abstract     = {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.},
      keywords     = {Antibodies, Bispecific (NLM Chemicals) / Antibodies,
                      Monoclonal, Humanized (NLM Chemicals) / CD22 protein, human
                      (NLM Chemicals) / Forkhead Transcription Factors (NLM
                      Chemicals) / Homeodomain Proteins (NLM Chemicals) / Il2rg
                      protein, mouse (NLM Chemicals) / Immunoconjugates (NLM
                      Chemicals) / Immunoglobulins, Intravenous (NLM Chemicals) /
                      Interleukin Receptor Common gamma Subunit (NLM Chemicals) /
                      Radioisotopes (NLM Chemicals) / Sialic Acid Binding Ig-like
                      Lectin 2 (NLM Chemicals) / Whn protein (NLM Chemicals) /
                      RAG-1 protein (NLM Chemicals) / Rituximab (NLM Chemicals) /
                      Lutetium (NLM Chemicals)},
      cin          = {D120 / G010 / G130 / E060},
      ddc          = {570},
      cid          = {I:(DE-He78)D120-20160331 / I:(DE-He78)G010-20160331 /
                      I:(DE-He78)G130-20160331 / I:(DE-He78)E060-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27524505},
      doi          = {10.1016/j.canlet.2016.08.007},
      url          = {https://inrepo02.dkfz.de/record/132842},
}