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Therapeutic enhancement of IL-2 through molecular design.

Author(s): Cassell DJ, Choudhri S, Humphrey R, Martell RE, Reynolds T, Shanafelt AB

Affiliation(s): Research Department, Biotechnology, Pharmaceutical Division, Bayer Corporation, 800 Dwight Way, Berkeley, CA 94701, USA. delanie.cassell.b@bayer.com

Publication date & source: 2002, Curr Pharm Des., 8(24):2171-83.

Publication type: Review

A recombinant human IL-2 analog (rIL-2, Proleukin) is currently being evaluated for clinical benefit in HIV infected patients. It is approved for therapy of patients with metastatic melanoma and renal cell carcinoma. Treatment of cancer patients with rIL-2 results in durable responses but is associated with life-threatening toxicity, which limits its use to patients in relatively good health. Antitumor efficacy associated with rIL-2 therapy are hypothesized to be mediated by distinct types of cells that express structurally different forms of the IL-2 receptor. This hypothesis suggests that it might be possible to engineer an IL-2 variant addressing the risks associated with the therapeutic use of IL-2. In this article, we review the clinical experience with IL-2 and its analogs, the evidence that different IL-2 receptors may dissociate efficacy and toxicity, and describe the generation of a novel IL-2 variant with the potential for a superior therapeutic index.

Page last updated: 2006-01-31

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