Summary:Aldesleukin is a modified recombinant interleukin-2 (IL-2) that is produced in E. coli. Although the in vitro biological activities of aldesleukin, such as enhancement of lymphocyte mitogenesis, induction of cytotoxic activity of lymphocytes, natural killer cells, and lymphokine-activated killer cells, have been found to be equivalent to those of native, physiologic IL-2, it differs chemically in two amino acids and it is not glycosylated. In vivo it causes immune activation characterized by marked lymphocytosis, eosinophilia, thrombocytopenia, and the upregulation of cytokines including IL-1, TNF, and g-interferon.
Aldesleukin was approved in 1993 for treatment of metastatic renal cell carcinoma and in 1998 for the metastatic melanoma. In both diseases, a small number of patients (~15%) showed partial or complete responses. The mechanism of its in vivo anti-tumor effect is not understood.
Aldesleukin has been investigated in several other diseases including acute myelogenous leukemia, non-Hodgkin’s lymphoma, HIV infection and Kaposi’s sarcoma.
Aldesleukin administration is often accompanied by severe adverse reactions involving the cardiac, pulmonary, GI and nervous systems, as well as capillary leak syndrome, exacerbations of autoimmune diseases, disseminated infections, and delayed reactions to contrast media. It has Pregnancy Category C.
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1. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-2116. http://www.ncbi.nlm.nih.gov/pubmed/10561265
2. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-696. http://www.ncbi.nlm.nih.gov/pubmed/7884429
3. Weiss GR, Grosh WW, Chianese-Bullock KA, Zhao Y, Liu H, Slingluff CL, Jr., et al. Molecular insights on the peripheral and intratumoral effects of systemic high-dose rIL-2 (aldesleukin) administration for the treatment of metastatic melanoma. Clin Cancer Res. 2011 Dec 1;17(23):7440-7450. http://www.ncbi.nlm.nih.gov/pubmed/21976537
4. Clement J, McDermott D. The high-dose aldesleukin (IL-2) "select" trial: a trial designed to prospectively validate predictive models of response to high-dose IL-2 treatment in patients with metastatic renal cell carcinoma. Clinical genitourinary cancer. 2009;7(2):9. http://www.ncbi.nlm.nih.gov/pubmed/19692326
5. McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI, Sosman JA et al. The High-Dose Aldesleukin "Select" Trial: A Trial to Prospectively Validate Predictive Models of Response Treatment in Patients with Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2014 Nov 25. http://www.ncbi.nlm.nih.gov/pubmed/25424850
6. McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI et al. The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015 Feb 1;21(3):561-8. http://www.ncbi.nlm.nih.gov/pubmed/25424850
7. Kim N, Jeon YW, Nam YS, Lim JY, Im KI, Lee ES, Cho SG. Therapeutic potential of low-dose IL-2 in a chronic GVHD patient by in vivo expansion of regulatory T cells. Cytokine. 2016 Feb;78:22-6. https://www.ncbi.nlm.nih.gov/pubmed/26624506