Abstract
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.
Keywords: il-2, interleukin2, molecular design, recombinant interleukin, hiv infection
Current Pharmaceutical Design
Title: Therapeutic Enhancement of IL-2 Through Molecular Design
Volume: 8 Issue: 24
Author(s): Delanie J. Cassell, Shurjeel Choudhri, Rachel Humphrey, Robert E. Martell, Theresa Reynolds and Armen B. Shanafelt
Affiliation:
Keywords: il-2, interleukin2, molecular design, recombinant interleukin, hiv infection
Abstract: 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.
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Cite this article as:
Cassell J. Delanie, Choudhri Shurjeel, Humphrey Rachel, Martell E. Robert, Reynolds Theresa and Shanafelt B. Armen, Therapeutic Enhancement of IL-2 Through Molecular Design, Current Pharmaceutical Design 2002; 8 (24) . https://dx.doi.org/10.2174/1381612023393260
DOI https://dx.doi.org/10.2174/1381612023393260 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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