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Treatment of central nervous system lymphoma in rats with intraventricular rituximab and serum

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Abstract

B cell lymphomas often develop in the central nervous system (CNS). Although rituximab (RTX) has been widely used for most B cell lymphomas, the efficacy for CNS lymphomas has yet to be elucidated. A major concern is that RTX might not reach lymphoma lesions, and either the antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity might not substantially operate in the CNS environment. Here we investigated the potential usefulness of co-administering RTX and human serum intraventricularly in nude rats carrying human B cell lymphomas in the CNS. Raji, a CD20-positive lymphoma cell line, was inoculated into the cerebrum of F344 (rnu/rnu) nude rats. After several days, RTX and human serum were delivered into the ipsilateral lateral ventricle via a cannula. Intraventricularly administered RTX was localized specifically at the lymphoma lesions, indicating that RTX penetrated the ependymal layer of the lateral ventricle to reach the tumor lesion, where it specifically bound to the lymphoma cells. The combination of RTX and serum (n = 12), but not RTX alone (n = 13), significantly extended the survival of the rats (P = 0.049). Intraventricular administration of RTX and serum in a rat/human CNS lymphoma model might be a potential novel treatment for CNS lymphomas of B cell origin. Clinical trials are warranted.

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Acknowledgments

We thank Dr. J. Usui and Ms. K. Noguchi (University of Tsukuba) for technical assistance with immunohistochemistry; Drs. T. Yamamoto, W. Tsuruta, and T. Tsurubuchi (University of Tsukuba) for technical advice with the rat surgical experiments and brain stereotaxic apparatus; and Drs. T. Sakurai (current affiliation, Kanazawa University) and T. Matsuki (current affiliation, University of Texas Southwestern Medical Center at Dallas) for technical assistance with the rat cannulation. This work was supported by the Aichi Cancer Research Foundation (Y. O.) and Research Grant of the Princess Takamatsu Cancer Research Fund (S. C.).

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Authors and Affiliations

  1. Clinical and Experimental Hematology, Major of Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Yasuyuki Miyake, Yasushi Okoshi, Takayuki Machino & Shigeru Chiba

Authors
  1. Yasuyuki Miyake
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  2. Yasushi Okoshi
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  3. Takayuki Machino
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  4. Shigeru Chiba
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Correspondence to Yasushi Okoshi or Shigeru Chiba.

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Y. Miyake and Y. Okoshi contributed equally to this work.

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Miyake, Y., Okoshi, Y., Machino, T. et al. Treatment of central nervous system lymphoma in rats with intraventricular rituximab and serum. Int J Hematol 92, 474–480 (2010). https://doi.org/10.1007/s12185-010-0669-7

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  • DOI: https://doi.org/10.1007/s12185-010-0669-7

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