Lymphomagenesis in the severe combined immune deficient mouse engrafted with human lymphocytes: Clues towards the pathogenesis and treatment of AIDS lymphoma (Review)

Vijay P. Khatri, Robert A. Baiocchi, Zale P. Bernstein, Michael A. Caligiuri

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We have used the severe combined immune deficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBL) from normal donors seropositive for the Epstein-Barr virus (EBV) to study malignant lymphoproliferative disease (LPD) in the setting of immune efficiency. Administration of a daily, low dose of interleukin-2 interacts with murine natural killer (NK) cells and human CD8+ T cells to prevent the outgrowth of human EBV-LPD in this chimeric hu-PBL-SCID mouse model. We have demonstrated that, in the absence of IL-2, the outgrowth of EBV-LPD in the SCID mouse is associated with overproduction of human interleukin-10 (IL-10), that in turn enhances tumor cell survival and tumor cell growth. Finally, we have utilized the information gained from this chimeric mouse model to perform a phase I study of daily, prolonged low dose IL-2 administration in patients with HIV-associated malignancies. We can safely achieve effective concentrations of IL-2 in vivo associated with a significant increase in human NK cells. Importantly, this can be accomplished in the absence of significant clinical toxicity or consistent increase in the plasma HIV RNA level over time. A phase II national study of low dose IL-2 therapy in HIV-associated lymphoma is currently underway.

Original languageEnglish (US)
Pages (from-to)241-246
Number of pages6
JournalOncology Reports
Volume4
Issue number1 SUPPL.
StatePublished - 1997
Externally publishedYes

Keywords

  • AIDS lymphoma
  • SCID mouse

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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