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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents The Role of Target Therapy in the Treatment of Gastrointestinal Noncolorectal Cancers: Clinical Impact and Cost Consideration
Current Cancer Drug Targets Clinical Pharmacology of Non-Steroidal Anti-Inflammatory Drugs: A Review
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Effect of Lapachol on the Inhibition of Matrix Metalloproteinase Related to the Invasion of Human Fibrosarcoma Cells
Current Molecular Pharmacology Developing Histone Deacetylase Inhibitors as Anti-Cancer Therapeutics
Current Medicinal Chemistry Malignancy in Common Variable Immune Deficiency: Report of Two Rare Cases of Gastrointestinal Malignancy and a Review of the Literature
Cardiovascular & Hematological Disorders-Drug Targets Cell-free DNA: Characteristics, Detection and its Applications in Myocardial Infarction
Current Pharmaceutical Design Lanreotide and its Potential Applications in Polycystic Kidney and Liver Diseases
Current Topics in Medicinal Chemistry Progress Towards Recombinant Anti-Infective Antibodies
Recent Patents on Anti-Infective Drug Discovery Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine
Current Medicinal Chemistry EMT Blockage Strategies: Targeting Akt Dependent Mechanisms for Breast Cancer Metastatic Behaviour Modulation
Current Gene Therapy Current Biomarkers for Lung Cancer
Current Signal Transduction Therapy Interleukin-18: Biology and Role in the Immunotherapy of Cancer
Current Medicinal Chemistry Genitourinary Tract Tumors in Children: An Update
Current Pediatric Reviews ABC Transporters in the Development of Multidrug Resistance in Cancer Therapy
Current Pharmaceutical Design Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy
Current Medicinal Chemistry III. Angiogenesis: Complexity of Tumor Vasculature and Microenvironment
Current Pharmaceutical Design Alterations in Glucose Metabolism in Alzheimer's Disease
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Clinical Use of Therapies Targeting Tumor Vasculature and Stroma
Current Cancer Drug Targets