gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Efficient killing of CD22+ tumor cells by a humanized diabody-RNase fusion protein

Meeting Abstract

  • corresponding author presenting/speaker Jürgen Krauss - Universitätsklinikum , Essen, Deutschland
  • Michaela A.E. Arndt - Universitätsklinikum , Essen
  • Bang K. Vu - National Cancer Institute at Frederick, Frederick, USA
  • Andrew C.R. Martin - University College London, London, UK
  • Huaitian Liu - National Cancer Institute at Frederick, Frederick, USA
  • Dianne L. Newton - National Cancer Institute at Frederick, Frederick, USA
  • Siegfried Seeber - Universitätsklinikum , Essen
  • Susanna M. Rybak - National Cancer Institute at Frederick, Frederick, USA
  • Juergen Krauss - Universitätsklinikum , Essen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP432

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Veröffentlicht: 20. März 2006

© 2006 Krauss et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



CD22-specific immunotoxins are highly potent drugs for the treatment of patients with refractory B-cell non-Hodgkin’s lymphoma. However, systemic toxicity and immunogenicity hamper the wide clinical application of these powerful reagents in cancer patients. To overcome these limitations we have developed a dimeric CD22-specific immunoenzyme capable of simultaneously delivering two RNase effector domains on one molecule to CD22+ tumor cells. As targeting moiety we first generated a highly stable humanized scFv by grafting the specificity of the clinically established anti-CD22 mAb RFB4 into robust, pre-selected frameworks from a human antibody phage display library. A derived diabody with further engineered interface (VL36Leu->Tyr) retained the same high affinity as the murine anti-CD22 mAb RFB4 (KD = 0.2 nM) as well as full antigen binding after 8 days of incubation in human serum at 37°C. A dimeric immunoenzyme comprising this diabody and Rana pipiens liver ribonuclease I (rapLRI) was generated, expressed as soluble protein in bacteria, and purified to homogeneity. The dimeric fusion protein killed several CD22+ tumor cell lines with high efficacy (IC50 = 3-20 nM) and exhibited 9-48-fold stronger cytotoxicity than a monovalent rapLRI-scFv counterpart. Our results suggest dimeric antibody-ribonuclease fusion proteins as potent immunotherapeutic reagents with presumably large therapeutic index.

Figure 1 [Fig. 1]