title: Treatment of AIDS-related Kaposi's sarcoma with interleukin-12: rationale and preliminary evidence of clinical activity.
abstract: 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-gamma), 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.
authors.affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA. yarchoan@helix.nih.gov
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.forename: James M
authors.initials: JM
authors.lastname: Pluda
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Rodriguez-Chavez
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Catanzaro
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000276:immunology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006566:Herpesviridae Infections / Q000453:epidemiology; D019288:Herpesvirus 8, Human / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D018664:Interleukin-12; D004317:Doxorubicin