Suppression of Human Lymphoma Development in the Severe Combined Immune-Deficient Mouse by Imexon Therapy

Abstract

Severe combined immune-deficient (SCID) mice accept human cell xenografts. SCID mice inoculated intraperitoneally with human peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors develop a form of disseminated human large cell lymphoma similar to that seen in transplant recipients and AIDS patients. Imexon (4-imino-1,4-diazobicyclo-3.1.0-hexan-2-one), a cyanoziridine immunomodulator with a selective inhibitory effect on B cells, was tested for its effect on this lymphoma development. Imexon started 2 weeks after PBMC inoculation significantly reduced the number of animals with lymphoma and the number of lymphomas sites per animal. The lymphoma was widely metastatic in the control animals but limited to the peritoneal cavity in the treated animals. Morphological and molecular parameters were used to confirm the reduced takes in the treated animals. Imexon was not myelosuppressive as determined by measurement of white blood cell counts. Imexon did not significantly suppress human IgG levels in the animals' serum. The tumor growth and lethality of human B lymphoblastoid cell lines in SCID mice was also suppressed by imexon treatment. A relatively nontoxic class of drugs that can suppress the development and/or growth of EBV-related lymphoma should be explored with priority for potential use in patients at high risk of this type of lymphoma.