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: Robert Yarchoan, James M Pluda, Kathleen M Wyvill, Karen Aleman, Isaac R Rodriguez-Chavez, Giovanna Tosato, Andrew T Catanzaro, Seth M Steinberg, Richard F Little
• Journal: Critical reviews in immunology (Crit Rev Immunol) Vol. 27 Issue 5 Pg. 401-14 ( 2007) ISSN: 1040-8401 [Print] United States
• PMID: 18197804 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Review)

Chemical References

• Anti-HIV Agents
• Antibiotics, Antineoplastic
• Cytokines
• Interleukin-12
• Doxorubicin

Topics

• AIDS-Related Opportunistic Infections (drug therapy, immunology)
• Anti-HIV Agents (administration & dosage, therapeutic use)
• Antibiotics, Antineoplastic (administration & dosage, therapeutic use)
• Antiretroviral Therapy, Highly Active
• Clinical Trials as Topic
• Cytokines (immunology, metabolism)
• Doxorubicin (administration & dosage, therapeutic use)
• HIV Infections (complications, drug therapy, immunology)
• HIV-1
• Herpesviridae Infections (epidemiology)
• Herpesvirus 8, Human (physiology)
• Humans
• Interleukin-12 (administration & dosage, adverse effects, immunology, therapeutic use)
• Sarcoma, Kaposi (drug therapy, epidemiology, immunology, virology)