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American Journal of Clinical Dermatology 2000Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through... (Review)
Review
Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment. In patients with IL-2R-positive cutaneous T cell lymphoma (CTCL), the overall response rate was 23 and 36%, respectively, after denileukin diftitox 9 or 18 micrograms/kg/day for 5 days every 3 weeks and was 37% in a dose-ranging trial. Quality of life (QOL) improved significantly in patients with CTCL who responded to treatment with denileukin diftitox 9 or 18 micrograms/kg/day compared with QOL at baseline and in nonresponders. In a murine model of IL-2R-expressing malignancy, denileukin diftitox prolonged survival compared with controls. The most common adverse events reported in patients who received denileukin diftitox were hypoalbuminemia, fever/chills, acute hypersensitivity reactions, nausea/vomiting and asthenia. Vascular leak syndrome has occurred during denileukin diftitox therapy. Antibody titers to denileukin diftitox occur in most patients after treatment but the presence of antibodies does not preclude a clinical response.
Topics: Animals; Antineoplastic Agents; Diphtheria Toxin; Humans; Interleukin-2; Lymphoma, T-Cell, Cutaneous; Recombinant Fusion Proteins; Skin Neoplasms
PubMed: 11702307
DOI: 10.2165/00128071-200001010-00008 -
Expert Opinion on Biological Therapy Nov 2009To review FDA approved and other potential uses of Ontak, denileukin diftitox. (Review)
Review
OBJECTIVE
To review FDA approved and other potential uses of Ontak, denileukin diftitox.
METHODS
Information was obtained via the internet and a journal literature review.
RESULTS
In 1999, the FDA approved the use of denileukin diftitox for patients with persistent or relapsed CD25-positive cutaneous T-cell lymphoma (CTCL), but Ontak has been reported to be an effective therapy for other neoplastic and non-neoplastic conditions. Oncological uses include therapy for CD25-negative T-cell lymphoma, recurrent and refractory chronic lymphocytic leukemia (CLL), non-Hodgkin's B-cell lymphoma (NHL), and human T-cell lymphotropic virus- 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL). Potential additional uses of Ontak include: therapy of graft-versus-host disease (GvHD) and autoimmune conditions, including psoriasis, rheumatoid arthritis (RA), systemic lupus, scleroderma and vasculitis. Denileukin diftitox's effect has also been studied for patients with hepatocellular carcinoma (HCC) and HIV, but conclusive data are still pending.
CONCLUSION
There are many potential uses for denileukin diftitox, in both malignant and benign disorders. More human trials are needed to demonstrate further efficacy for a wide range of diseases.
Topics: Antineoplastic Agents; Diphtheria Toxin; Humans; Interleukin-2; Lymphoma, T-Cell; Recombinant Fusion Proteins; United States; United States Food and Drug Administration
PubMed: 19817678
DOI: 10.1517/14712590903348135 -
Expert Review of Anticancer Therapy Feb 2005Denileukin diftitox (DAB389IL-2; Ontak) is a novel recombinant fusion protein approved by the US Food and Drug Administration for the treatment of relapsed or refractory... (Review)
Review
Denileukin diftitox (DAB389IL-2; Ontak) is a novel recombinant fusion protein approved by the US Food and Drug Administration for the treatment of relapsed or refractory cutaneous T-cell lymphoma. It consists of fragments of diphtheria toxin linked to human interleukin-2 and works by targeting the high-affinity interleukin-2 receptor expressed on malignant cells. This article will review the clinical trials leading to the approval of denileukin diftitox for cutaneous T-cell lymphoma, and discuss the potential future role of this novel drug in patients with both malignant and nonmalignant diseases, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, solid tumors, psoriasis and graft-versus-host disease.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Diphtheria Toxin; Graft vs Host Disease; Humans; Interleukin-2; Leukemia, Lymphocytic, Chronic, B-Cell; Lung Neoplasms; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Cutaneous; Psoriasis; Recombinant Fusion Proteins; Survival
PubMed: 15757436
DOI: 10.1586/14737140.5.1.33 -
Cancer Investigation Sep 2007Denileukin diftitox (DAB(389)IL-2; Ontak) is a cytotoxic fusion protein designed to target cells expressing the receptor for interleukin-2 (IL-2). It has been approved... (Review)
Review
Denileukin diftitox (DAB(389)IL-2; Ontak) is a cytotoxic fusion protein designed to target cells expressing the receptor for interleukin-2 (IL-2). It has been approved for treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor, but more recent data indicate activity in the setting of not only T-cell but also B-cell malignancies. This review will update the experience to date of denileukin diftitox in T- and B-cell malignancies.
Topics: Antineoplastic Agents; Diphtheria Toxin; Female; Humans; Interleukin-2; Lymphoma; Male; Recombinant Fusion Proteins
PubMed: 17882663
DOI: 10.1080/07357900701360096 -
Clinical Journal of Oncology Nursing Apr 2004Non-Hodgkin's lymphoma (NHL) is a complex group of hematologic malignancies. The majority are B-cell lineage, with 10%-20% arising from T-cell lineage. Detailed... (Review)
Review
Non-Hodgkin's lymphoma (NHL) is a complex group of hematologic malignancies. The majority are B-cell lineage, with 10%-20% arising from T-cell lineage. Detailed knowledge of the subtypes and staging of NHL is essential to plan treatment and provide effective management of treatment-related side effects. Although numerous regimens have demonstrated efficacy in the treatment of NHL, some subtypes of lymphomas generally are not curable. The recent development of targeted therapies such as denileukin diftitox (Ontak, Ligand Pharmaceuticals, Inc., San Diego, CA) has resulted in potentially significant advances in the treatment of NHL. Oncology nurses must gain a better understanding of the unique mechanism of action of this agent and its side effects to successfully manage patients being treated with this novel therapy.
Topics: Antineoplastic Agents; Diphtheria Toxin; Humans; Interleukin-2; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Recombinant Fusion Proteins
PubMed: 15108419
DOI: 10.1188/04.CJON.169-174 -
CEN Case Reports Feb 2023Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and...
Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and hypoalbuminemia. This condition is caused by leakage of plasma and proteins into the extravascular space and can be classified as either idiopathic or secondary. Secondary systemic capillary leak syndrome can result from cancer, infections, medications, or surgery. Systemic capillary leak syndrome frequently develops as a side effect of denileukin diftitox treatment of refractory cutaneous T-cell lymphoma. However, the pathophysiology of this disease is not well understood. Herein, we report a case of denileukin diftitox-induced systemic capillary leak syndrome.
Topics: Humans; Capillary Leak Syndrome; Interleukin-2; Skin Neoplasms; Acute Kidney Injury
PubMed: 35870043
DOI: 10.1007/s13730-022-00720-3 -
Seminars in Oncology Feb 2006Denileukin diftitox (ONTAK; Seragen Inc, San Diego, CA) is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that overexpress the... (Review)
Review
Denileukin diftitox (ONTAK; Seragen Inc, San Diego, CA) is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that overexpress the IL-2 receptor. The human IL-2 receptor exists in three isoforms: low (CD25), intermediate (CD122/CD132), and high (CD25/CD122/CD132) affinity. The high-affinity form of this receptor is expressed on activated T lymphocytes, activated B lymphocytes, and activated macrophages. A number of leukemias and lymphomas, including cutaneous T-cell lymphoma, chronic lymphocytic leukemia, and B-cell non-Hodgkin's lymphoma, express a component of the receptor. Ex vivo studies have shown that denileukin diftitox interacts with the high- and intermediate-affinity IL-2 receptor on the cell surface and undergoes internalization. Subsequent cleavage in the endosome releases the diphtheria toxin into the cytosol, which then inhibits cellular protein synthesis, resulting in rapid cell death. This article examines the clinical profile and potential benefits of denileukin diftitox in the treatment of cutaneous T-cell lymphoma and other hematologic disorders.
Topics: Antineoplastic Agents; Diphtheria Toxin; Graft vs Host Disease; Humans; Interleukin-2; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Neoplasms; Receptors, Interleukin-2; Recombinant Fusion Proteins
PubMed: 16516670
DOI: 10.1053/j.seminoncol.2005.12.017 -
Future Oncology (London, England) Aug 2008Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of... (Review)
Review
Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of diphtheria toxin linked to human IL-2. Denileukin diftitox specifically binds to IL-2 receptors on the cell membrane, is internalized via receptor-mediated endocytosis and inhibits protein synthesis by ADP ribosylation of elongation factor 2, resulting in cell death. This article focuses on the clinical trial that led to the US FDA approval of the drug for cutaneous T-cell lymphoma in 1999, and other investigational studies for hematologic malignancies, recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin B-cell lymphoma, graft-versus-host disease and autoimmune disease, demonstrating the activity and adverse effects of the drug.
Topics: Antineoplastic Agents; Capillary Leak Syndrome; Clinical Trials as Topic; Diphtheria Toxin; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Interleukin-2; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Neoplasms; Protein Synthesis Inhibitors; Receptors, Interleukin-2; Recombinant Fusion Proteins; T-Lymphocytes, Regulatory; Thyrotoxicosis
PubMed: 18684057
DOI: 10.2217/14796694.4.4.457