Aldesleukin

Identification

Summary

Aldesleukin is a recombinant analog of interleukin-2 used to induce an adaptive immune response in the treatment of renal cell carcinoma.

Brand Names

Proleukin

Generic Name

Aldesleukin

DrugBank Accession Number

DB00041

Background

Aldesleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human interleukin-2. This recombinant form differs from native interleukin-2 in the following ways: a) Aldesleukin is not glycosylated because it is derived from E. coli; b) the molecule has no N-terminal alanine; the codon for this amino acid was deleted during the genetic engineering procedure; c) the molecule has serine substituted for cysteine at amino acid position 125.

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Interleukin-based products

Protein Structure

Protein Chemical Formula

C₆₉₀H₁₁₁₅N₁₇₇O₂₀₂S₆

Protein Average Weight

15314.8 Da

Sequences

>Aldesleukin (CS373812.1 Sequence 2 from Patent EP1688146)
MPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE
EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR
WITFSQSIISTLT

References:

1. NCBI: CS373812.1 [Link]

Download FASTA Format

Synonyms

• 125-L-serine-2-133-interleukin 2 (human reduced)
• Aldesleukin
• Aldesleukina
• ILT-101
• ILT101
• Interleukin-2 aldesleukin
• Interleukin-2(2-133),125-ser
• Recombinant human interleukin-2
• Recombinant interleukin-2 human

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Pharmacology

Indication

For treatment of adults with metastatic renal cell carcinoma.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Metastatic melanoma		••••••••••••	•••••		•••••••••
Treatment of	Metastatic renal cell carcinoma		••••••••••••	•••••		•••••••••

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Pharmacodynamics

Used to treat renal cell carcinoma, Aldesleukin induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.

Mechanism of action

Aldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate growth and differentiation of T cells.

Target	Actions	Organism
AInterleukin-2 receptor subunit beta	agonist modulator	Humans
AInterleukin-2 receptor subunit alpha	agonist modulator	Humans
ACytokine receptor common subunit gamma	agonist	Humans

Absorption

Not Available

Volume of distribution

0.18 l/kg

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

The pharmacokinetic profile of Proleukin is characterized by high plasma concentrations following a short IV infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive protein excreted in the urine. Following the initial rapid organ distribution, the primary route of clearance of circulating proleukin is the kidney. Greater than 80% of the amount of Proleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolized to amino acids in the cells lining the proximal convoluted tubules.

Half-life

13 min-85 min

Clearance

Not Available

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Aldesleukin may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abaloparatide	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Abaloparatide.
Abatacept	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Aldesleukin.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Aldesleukin.

Food Interactions

No interactions found.

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Proleukin	Powder, for solution	22000000 unit / vial	Intravenous	Sterimax Inc	1995-12-31	Not applicable
Proleukin	Injection	1.1 mg/1mL	Intravenous	Novartis	1992-05-06	2017-01-01
Proleukin	Injection, powder, lyophilized, for solution	1.1 mg/1mL	Intravenous	Clinigen Limited	1992-05-05	Not applicable
Proleukin	Injection	1.1 mg/1mL	Intravenous	Physicians Total Care, Inc.	2006-05-22	2011-06-30
Proleukin	Injection, powder, lyophilized, for solution	1.1 mg/1mL	Intravenous	Iovance Biotherapeutics, Inc	1992-05-05	Not applicable

Categories

ATC Codes

L03AC01 — Aldesleukin

• L03AC — Interleukins
• L03A — IMMUNOSTIMULANTS
• L03 — IMMUNOSTIMULANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Adjuvants, Immunologic
• Amino Acids, Peptides, and Proteins
• Anti-HIV Agents
• Anti-Infective Agents
• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• Biological Factors
• Cancer immunotherapy
• Cytochrome P-450 CYP2E1 Inhibitors
• Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
• Cytochrome P-450 Enzyme Inhibitors
• Cytokines
• Drugs that are Mainly Renally Excreted
• Hypotensive Agents
• Immunosuppressive Agents
• Immunotherapy
• Increased Lymphocyte Activation
• Increased Lymphocyte Cell Production
• Intercellular Signaling Peptides and Proteins
• Interleukins
• Lymphocyte Growth Factor
• Lymphokines
• Myelosuppressive Agents
• Narrow Therapeutic Index Drugs
• Peptides
• Proteins

Chemical TaxonomyProvided by Classyfire

Description

Not Available

Kingdom

Organic Compounds

Super Class

Organic Acids

Class

Carboxylic Acids and Derivatives

Sub Class

Amino Acids, Peptides, and Analogues

Direct Parent

Peptides

Alternative Parents

Not Available

Substituents

Not Available

Molecular Framework

Not Available

External Descriptors

Not Available

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

M89N0Q7EQR

CAS number

110942-02-4

References

Synthesis Reference

Hans-Ake Fabricius, Roland Stahn, "Serum-free and mitogen-free T-cell growth factor and process for making same." U.S. Patent US4464355, issued May, 1971.

US4464355

General References

1. PROLEUKIN® (aldesleukin) FDA label [Link]

External Links

UniProt

P60569

Genbank

M11144

PubChem Substance

46508054

RxNav

70223

ChEMBL

CHEMBL1201438

Therapeutic Targets Database

DAP001099

PharmGKB

PA448081

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Interleukin_2

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Acute Myeloid Leukemia	1
4	Completed	Treatment	Metastatic Melanoma / Metastatic Renal Cell Carcinoma ( mRCC)	1
4	Completed	Treatment	Renal Cancer	1
4	Terminated	Other	Metastatic Melanoma	1
4	Terminated	Treatment	Liver Disease / Transplantations	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

• Bayer Healthcare
• Chiron Corp.
• Novartis AG
• Physicians Total Care Inc.
• Prometheus Laboratories Inc.

Dosage Forms

Form	Route	Strength
Injection	Intravenous	1.1 mg/1mL
Injection, powder, for solution	Parenteral; Subcutaneous	18000.000 UI/ML
Injection, powder, lyophilized, for solution	Intravenous	1.1 mg/1mL
Powder, for solution	Intravenous	22000000 unit / vial
Injection, powder, for solution	Parenteral
Injection, powder, lyophilized, for solution	Intravenous	1.1 mg/ml
Injection, powder, for solution	Intravenous	18 miu

Prices

Unit description	Cost	Unit
Proleukin 22 million unit vial	1092.34USD	each
Proleukin 22000000 unit Solution Vial	976.66USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
hydrophobicity	-0.192	Not Available
isoelectric point	7.31	Not Available

Targets

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Details1. Interleukin-2 receptor subunit beta

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Agonist

Modulator

General Function

Interleukin-2 receptor activity

Specific Function

Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.

Gene Name

IL2RB

Uniprot ID

P14784

Uniprot Name

Interleukin-2 receptor subunit beta

Molecular Weight

61116.59 Da

References

1. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA: Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. [Article]
2. Steppan S, Eckart MR, Bajsarowicz K, Sternberg LR, Greve JM, Cassell DJ: Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. J Interferon Cytokine Res. 2006 Mar;26(3):171-8. [Article]
3. Cornish GH, Sinclair LV, Cantrell DA: Differential regulation of T-cell growth by IL-2 and IL-15. Blood. 2006 Jul 15;108(2):600-8. Epub 2006 Mar 28. [Article]
4. Lee KD, Chen HW, Chen CC, Shih YC, Liu HK, Cheng ML: Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2. Oncol Rep. 2006 May;15(5):1211-6. [Article]
5. Maclennan C, Hutchinson P, Holdsworth S, Bardin PG, Freezer NJ: Airway inflammation in asymptomatic children with episodic wheeze. Pediatr Pulmonol. 2006 Jun;41(6):577-83. [Article]
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Details2. Interleukin-2 receptor subunit alpha

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Agonist

Modulator

General Function

Interleukin-2 receptor activity

Specific Function

Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autorea...

Gene Name

IL2RA

Uniprot ID

P01589

Uniprot Name

Interleukin-2 receptor subunit alpha

Molecular Weight

30818.915 Da

References

1. Waldmann TA: Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol. 2007 Jan;27(1):1-18. Epub 2007 Jan 11. [Article]
2. Recchia F, Cesta A, Rea S: Low dose interleukin-2 and 13-cis-retinoic acid as maintenance therapy in patients with solid tumors responsive to chemotherapy. J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):135-43. [Article]
3. Waldmann TA: Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene. 2007 May 28;26(25):3699-703. [Article]
4. Vlad G, Ho EK, Vasilescu ER, Fan J, Liu Z, Cai JW, Jin Z, Burke E, Deng M, Cadeiras M, Cortesini R, Itescu S, Marboe C, Mancini D, Suciu-Foca N: Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation. Transpl Immunol. 2007 Jul;18(1):13-21. Epub 2007 Apr 2. [Article]
5. Liu BY, Zhu P, Luo HB, Fu N: [Screening of short peptides binding to cell surface interleukin-2 receptor alpha chain]. Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jul;26(7):971-4. [Article]
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
7. Ouyang Y, Kaminski NE: Phospholipase A2 inhibitors p-bromophenacyl bromide and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes. Arch Toxicol. 1999 Feb;73(1):1-6. [Article]

Details3. Cytokine receptor common subunit gamma

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Agonist

General Function

Interleukin-2 binding

Specific Function

Common subunit for the receptors for a variety of interleukins.

Gene Name

IL2RG

Uniprot ID

P31785

Uniprot Name

Cytokine receptor common subunit gamma

Molecular Weight

42286.68 Da

References

1. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA: Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. [Article]
2. Shibata F, Toma T, Wada T, Inoue M, Tone Y, Ohta K, Kasahara Y, Sano F, Kimura M, Ikeno M, Koizumi S, Yachie A: Skin infiltration of CD56(bright) CD16(-) natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations. Eur J Haematol. 2007 Jul;79(1):81-5. [Article]
3. Fonseca SG, Reis MM, Coelho V, Nogueira LG, Monteiro SM, Mairena EC, Bacal F, Bocchi E, Guilherme L, Zheng XX, Liew FY, Higuchi ML, Kalil J, Cunha-Neto E: Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy. Scand J Immunol. 2007 Aug-Sep;66(2-3):362-71. [Article]
4. Blank RB, Lamb EW, Tocheva AS, Crow ET, Lim KC, McKerrow JH, Davies SJ: The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells. J Infect Dis. 2006 Dec 1;194(11):1609-16. Epub 2006 Oct 23. [Article]
5. Smyth CM, Ginn SL, Deakin CT, Logan GJ, Alexander IE: Limiting {gamma}c expression differentially affects signaling via the interleukin (IL)-7 and IL-15 receptors. Blood. 2007 Jul 1;110(1):91-8. Epub 2007 Mar 15. [Article]

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Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54