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Lymphoma

Improved therapy of non-Hodgkin's lymphoma xenografts using radionuclides pretargeted with a new anti-CD20 bispecific antibody

Leukemia volume 19, pages 1064–1069 (2005)Cite this article

Abstract

A comparison of the therapeutic efficacy of a new bispecific monoclonal antibody (bsMAb)-pretargeting system vs the conventional direct targeting modality was undertaken. A bsMAb was made by coupling the Fab′ of a humanized anti-CD20 antibody to the Fab′ of a murine antibody directed against the peptide histamine-succinyl-glycine (HSG). The tumor targeting of the bsMAb was separated from the subsequent delivery of the radionuclide-bearing HSG peptide conjugated with 111In or 90Y. Nude mice bearing s.c. Ramos human B-cell lymphomas were injected with the bsMAb and then, 48 h later, 111In/90Y-HSG peptide was given. At 3 h postinjection, tumor/blood ratios for pretargeted 111In-HSG-peptide were similar to that observed with the directly conjugated 111In-anti-CD20 IgG at its highest level on day 7, but by day 1, tumor/blood ratios were about 10-fold higher than the IgG. Tumors progressed rapidly in animals given 800 μCi of 90Y-HSG peptide alone, whereas 5/10 animals in the group pretargeted by the anti-CD20 bsMAb were tumor-free 18 weeks later. The antitumor response in animals administered the pretargeted 90Y-HSG peptide was also significantly superior to treatment with the directly radiolabeled 90Y-anti-CD20 IgG, whether given as a single injection (P<0.007) or as a divided dose (P=0.016). This bsMAb-pretargeting procedure significantly improves the therapeutic response of targeted radionuclides in non-Hodgkin's lymphoma, warranting further development of this method of radioimmunotherapy.

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Acknowledgements

We thank Jessica Kearney, Gaik-lin Ong, Mr Guy Newsome, Mr Dion Yeldell, and Dr Li Zeng for their technical assistance. We also thank Ms Agatha Sheering for providing the DOTA-IMMU-106 IgG and Dr Michele Losman for the anti-iditype antibody to IMMU-106. This work was supported in part by the Office of Science (BER), US Department of Energy Grant DE-FG02-95ER62028 (RMS) and a grant from the Thomas and Agnes Carvel Foundation awarded to the Garden State Cancer Center.

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Authors and Affiliations

  1. Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ, USA

    R M Sharkey, H Karacay & D M Goldenberg

  2. IBC Pharmaceuticals Inc., Morris Plains, NJ, USA

    C-H Chang

  3. Immunomedics Inc., Morris Plains, NJ, USA

    W J McBride & I D Horak

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  1. R M Sharkey
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  2. H Karacay
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  4. W J McBride
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  5. I D Horak
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  6. D M Goldenberg
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Correspondence to D M Goldenberg.

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Supplementary Information accompanies the paper on Leukemia website (http://www.nature.com/leu).

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Sharkey, R., Karacay, H., Chang, CH. et al. Improved therapy of non-Hodgkin's lymphoma xenografts using radionuclides pretargeted with a new anti-CD20 bispecific antibody. Leukemia 19, 1064–1069 (2005). https://doi.org/10.1038/sj.leu.2403751

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