Treatment of Central Nervous System Lymphoma in Rats with Intraventricular Rituximab and Serum

Overview

Journal Int J Hematol

Specialty Hematology

Date 2010 Sep 8

PMID 20820968

Citations 1

Authors

Yasuyuki Miyake

Yasushi Okoshi

Takayuki Machino

Shigeru Chiba

Affiliations

Soon will be listed here.

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.

Citing Articles

Monitoring of the Complement System Status in Patients With B-Cell Malignancies Treated With Rituximab.

Felberg A, Taszner M, Urban A, Majeranowski A, Jaskula K, Jurkiewicz A Front Immunol. 2020; 11:584509.

PMID: 33329558 PMC: 7710700. DOI: 10.3389/fimmu.2020.584509.

References

Byrd J, Kitada S, Flinn I, Aron J, Pearson M, Lucas D . The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction. Blood. 2002; 99(3):1038-43. DOI: 10.1182/blood.v99.3.1038. View

Golay J, Zaffaroni L, Vaccari T, Lazzari M, Borleri G, Bernasconi S . Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000; 95(12):3900-8. View

Yamanaka R, Morii K, Shinbo Y, Homma J, Sano M, Tsuchiya N . Results of treatment of 112 cases of primary CNS lymphoma. Jpn J Clin Oncol. 2008; 38(5):373-80. DOI: 10.1093/jjco/hyn027. View

Rubenstein J, Fridlyand J, Abrey L, Shen A, Karch J, Wang E . Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007; 25(11):1350-6. DOI: 10.1200/JCO.2006.09.7311. View

Einfeld D, Brown J, VALENTINE M, Clark E, Ledbetter J . Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains. EMBO J. 1988; 7(3):711-7. PMC: 454379. DOI: 10.1002/j.1460-2075.1988.tb02867.x. View

Stamenkovic I, Seed B . Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein. J Exp Med. 1988; 167(6):1975-80. PMC: 2189672. DOI: 10.1084/jem.167.6.1975. View

Hudson W, Li Q, Le C, Kersey J . Xenotransplantation of human lymphoid malignancies is optimized in mice with multiple immunologic defects. Leukemia. 1998; 12(12):2029-33. DOI: 10.1038/sj.leu.2401236. View

Havenith C, Askew D, Walker W . Mouse resident microglia: isolation and characterization of immunoregulatory properties with naïve CD4+ and CD8+ T-cells. Glia. 1998; 22(4):348-59. View

Shimazu Y, Notohara K, Ueda Y . Diffuse large B-cell lymphoma with central nervous system relapse: prognosis and risk factors according to retrospective analysis from a single-center experience. Int J Hematol. 2009; 89(5):577-83. DOI: 10.1007/s12185-009-0289-2. View

10.

Shimadoi S, Takami A, Kondo Y, Okumura H, Nakao S . Macrophage colony-stimulating factor enhances rituximab-dependent cellular cytotoxicity by monocytes. Cancer Sci. 2007; 98(9):1368-72. PMC: 11160048. DOI: 10.1111/j.1349-7006.2007.00544.x. View

11.

Di Gaetano N, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E . Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol. 2003; 171(3):1581-7. DOI: 10.4049/jimmunol.171.3.1581. View

12.

de Lange EC , de Boer BA , Breimer . Microdialysis for pharmacokinetic analysis of drug transport to the brain. Adv Drug Deliv Rev. 2000; 36(2-3):211-227. DOI: 10.1016/s0169-409x(98)00089-1. View

13.

Johanson C, Duncan J, Stopa E, Baird A . Enhanced prospects for drug delivery and brain targeting by the choroid plexus-CSF route. Pharm Res. 2005; 22(7):1011-37. DOI: 10.1007/s11095-005-6039-0. View

14.

Pardridge W . Drug delivery to the brain. J Cereb Blood Flow Metab. 1997; 17(7):713-31. DOI: 10.1097/00004647-199707000-00001. View

15.

Griffiths G, Mattes M, Stein R, Govindan S, Horak I, Hansen H . Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res. 2003; 9(17):6567-71. View

16.

Kadoch C, Dinca E, Voicu R, Chen L, Nguyen D, Parikh S . Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model. Clin Cancer Res. 2009; 15(6):1989-97. PMC: 4372389. DOI: 10.1158/1078-0432.CCR-08-2054. View

17.

Belichenko P, Dickson P, Passage M, Jungles S, Mobley W, Kakkis E . Penetration, diffusion, and uptake of recombinant human alpha-L-iduronidase after intraventricular injection into the rat brain. Mol Genet Metab. 2005; 86(1-2):141-9. DOI: 10.1016/j.ymgme.2005.04.013. View

18.

van Meerten T, van Rijn R, Hol S, Hagenbeek A, Ebeling S . Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006; 12(13):4027-35. DOI: 10.1158/1078-0432.CCR-06-0066. View

19.

Schulz H, Pels H, Schmidt-Wolf I, Zeelen U, Germing U, Engert A . Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab. Haematologica. 2004; 89(6):753-4. View

20.

Pedersen I, Buhl A, Klausen P, Geisler C, Jurlander J . The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism. Blood. 2002; 99(4):1314-9. DOI: 10.1182/blood.v99.4.1314. View