Aldesleukin

Synonyms :
IL-2, Interleukin-2 precursor, T-cell growth factor, TCGF

Status : approved

Category

Antineoplastic Agents

Therapeutic Classification

IMMUNOSTIMULANTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSTIMULANTS
IMMUNOSTIMULANTS
Anti-HIV Agents

Description

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.

Used

For treatment of adults with metastatic renal cell carcinoma.

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.

Dosage

Form Route Strength
Injection intravenous 1.1 mg/mL
Injection, powder, lyophilized, for solution intravenous 1.1 mg/mL
Powder for solution intravenous 22000000 unit

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.

Half Life

13 min-85 min

Elimination Route

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.

Volume of Distribution

0.18 l/kg

Chemical Classification

Peptides

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

Chemical Name

IL-2

Brands

name Dosage form Country
Proleukin injection US
Proleukin powder for solution Canada
Proleukin injection, powder, lyophilized, for solution US

Drug Drug Interactions

  •  Alclometasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Amcinonide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Beclomethasone  : May diminish the antineoplastic effect of Aldesleukin.
  •  Betamethasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Budesonide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Butabarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Butethal  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Calcipotriol  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Clobetasol propionate  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Clocortolone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Clozapine  : Myelosuppressive Agents may enhance the adverse/toxic effect of Clozapine. Specifically, the risk for agranulocytosis may be increased.
  •  Corticotropin  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Cortisone acetate  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Desoximetasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Dexamethasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Diatrizoate  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Diflorasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Duloxetine  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Duloxetine.
  •  Ethiodized oil  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Fludrocortisone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Fluocinolone Acetonide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Fluocinonide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Fluorometholone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Flurandrenolide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Fluticasone furoate  : May diminish the antineoplastic effect of Aldesleukin.
  •  Halcinonide  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Halobetasol Propionate  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Heptabarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Hexobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Hydrocortamate  : May diminish the antineoplastic effect of Aldesleukin.
  •  Hydrocortisone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Interferon alfa-n3  : Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
  •  Interferon alfacon-1  : Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
  •  Iodipamide  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Iodixanol  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Iohexol  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Iopamidol  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Iopromide  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Ioversol  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Ioxilan  : May enhance the potential for allergic or hypersensitivity reactions to Iodinated Contrast Agents.
  •  Levodopa  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Levodopa.
  •  Metamizole  : May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
  •  Methohexital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Methylprednisolone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Mometasone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Peginterferon alfa-2a  : Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
  •  Peginterferon alfa-2b  : Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
  •  Pentobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Prednicarbate  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Prednisolone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Prednisone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Primidone  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Rimexolone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Risperidone  : Hypotensive Agents may enhance the hypotensive effect of Risperidone.
  •  Secobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Triamcinolone  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
  •  Vilanterol  : Corticosteroids may diminish the antineoplastic effect of Aldesleukin.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Interleukin-2 receptor subunit beta : in Human
  • Interleukin-2 receptor subunit alpha : in Human
  • Cytokine receptor common subunit gamma : in Human