Aldesleukin

Chemical Identity

Property	Value
Molecular Weight	~15.3 kDa
Amino Acids	133 (modified from native IL-2)
CAS Number	110942-02-4
Modifications	No Cys125, Ser125 substitution
Route	IV bolus, IV infusion

Structure

Aldesleukin (Proleukin) is recombinant human interleukin-2 (IL-2) produced in E. coli. It differs from native IL-2 by lacking the N-terminal alanine (position 1) and having serine substituted for cysteine at position 125, eliminating a disulfide bond. These modifications simplify production without affecting biological activity.

Mechanism of Action

Aldesleukin binds IL-2 receptors (IL-2R) on T cells, NK cells, and lymphokine-activated killer (LAK) cells, activating JAK1/JAK3 and STAT5 signaling. High-dose IL-2 stimulates massive T-cell and NK cell proliferation and activation, generating anti-tumor immune responses.

Clinical Applications

• Metastatic renal cell carcinoma: High-dose IL-2 (Proleukin)
• Metastatic melanoma: High-dose IL-2 therapy
• Complete responses: 5-10% durable complete responses in RCC and melanoma
• Lymphocyte therapy: Expansion for adoptive cell therapy

Pharmacokinetics

• Half-life: 85 minutes (IV bolus)
• Distribution: Vascular and extravascular
• Metabolism: Kidney (primary)
• Dosing: 600,000 IU/kg IV q8h x 14 doses (high-dose regimen)
• Route: IV bolus or continuous infusion

Safety and Side Effects

Capillary leak syndrome (dose-limiting), hypotension requiring vasopressors, pulmonary edema, renal dysfunction, cardiac arrhythmias, confusion, and multi-organ toxicity. Requires ICU-level monitoring. Treatment-related mortality ~2%.

References

• Fyfe, G., et al. (1993). High-dose IL-2 for metastatic RCC. Journal of Clinical Oncology, 13, 688-696.
• Atkins, M.B., et al. (1999). High-dose IL-2 for metastatic melanoma. Journal of Clinical Oncology, 17, 2105-2116.