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Critical Reviews™ in Immunology
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ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i5.10
pages 401-414

PART IV. Cytokine and Hormone Immunotherapy
Treatment of AIDS-Related Kaposi's Sarcoma with Interleukin-12: Rationale and Preliminary Evidence of Clinical Activity

Robert Yarchoan
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
James M. Pluda
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Kathleen M. Wyvill
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Karen Aleman
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Isaac R. Rodriguez-Chavez
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Giovanna Tosato
Laboratory of Cellular Oncology; Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Andrew T. Catanzaro
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Seth M. Steinberg
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA
Richard F. Little
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA

RÉSUMÉ

In this article, we review the preliminary evidence for the activity of interleukin-12 (IL−12) against Kaposi's sarcoma (KS) and discuss these results in the context of the biology of IL−12 and KS. IL−12 is a cytokine that enhances type 1 immunity, induces production of interferon gamma (IFN−γ), and mediates antiangiogenic effects. In addition, it can downregulate a constitutively active G protein coupled receptor that is encoded by Kaposi's sarcoma−associated herpesvirus, the causative agent of KS. These factors suggested that IL−12 might be worth exploring as a potential anti−KS agent. In an initial phase I pilot study, IL−12 was found to have anti−KS activity when used alone in patients with AIDS−associated KS who were on a stable regimen of antiretroviral therapy. In preliminary results from a subsequent study of the combination of IL−12 plus liposomal doxorubicin along with highly active antiretroviral therapy, remissions were obtained in a substantial percentage of patients with advanced AIDS−associated KS. IL−12 has also been found active in patients with certain lymphomas. These results suggest that IL−12 may be worth exploring further as a potential antitumor agent in selected tumors.


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