Treatment of AIDS-related Kaposi's sarcoma with interleukin-12: rationale and preliminary evidence of clinical activity.
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.
Yarchoan
Robert
R
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1868, USA. yarchoan@helix.nih.gov
Pluda
James M
JM
Wyvill
Kathleen M
KM
Aleman
Karen
K
Rodriguez-Chavez
Isaac R
IR
Tosato
Giovanna
G
Catanzaro
Andrew T
AT
Steinberg
Seth M
SM
Little
Richard F
RF
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
D019380:Anti-HIV Agents; D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D018664:Interleukin-12; D004317:Doxorubicin