Human interleukin-2

Summary

Human interleukin-2 (IL-2) is an endogenous cytokine critical for T-lymphocyte growth and immune regulation. Recombinant forms (e.g., aldesleukin) are FDA-approved for metastatic renal cell carcinoma and metastatic melanoma. High-dose IL-2 can induce durable responses in a subset of patients but carries significant toxicity, including capillary leak syndrome. Low-dose regimens and engineered IL-2 variants are under active investigation to improve the therapeutic window.

Mechanism of Action

Binds to the IL-2 receptor complex (IL-2Rα/β/γ, CD25/CD122/CD132) on T cells and NK cells, activating JAK1/JAK3 and STAT5 signaling pathways, promoting T-cell proliferation, differentiation, and survival; also stimulates NK cell cytotoxicity and supports regulatory T-cell homeostasis.

Routes of Administration

Goals & Uses

• Metastatic renal cell carcinoma treatmentOncologyHigh
• Immune reconstitution in HIVInfectious DiseaseModerate
• Metastatic melanoma treatmentOncologyHigh
• Expansion of regulatory T cells (autoimmune diseases)ImmunologyModerate
• Adoptive cell therapy adjunctOncology / ImmunotherapyModerate

Contraindications

• Active autoimmune disease requiring systemic treatmentImmunologyModerate
• Severe hepatic or renal impairmentOrgan ImpairmentModerate
• Active infection or sepsisInfectious DiseaseHigh
• Organ transplant recipients on immunosuppressionTransplantHigh
• Abnormal thallium stress test or pulmonary function testsCardiovascular/PulmonaryHigh

Adverse Effects

• Injection site reactionsLocalCommon
• Capillary leak syndromeVascularCommonLeakage of fluid from blood vessels into tissues
• HypotensionCardiovascularCommonLow blood pressure
• Neuropsychiatric effects (confusion, somnolence)NeurologicalUncommon
• Renal impairment / oliguriaRenalCommon
• Fever, chills, rigorsConstitutionalCommon

Drug Interactions

• Antihypertensive agentsModerate
• Nephrotoxic agents (e.g., aminoglycosides, NSAIDs)High
• CorticosteroidsHigh
• Checkpoint inhibitors (e.g., nivolumab, ipilimumab)Moderate

Population Constraints

• Patients with CNS metastasesDisease RelatedRelative
• Pediatric patientsAgeRelative
• Elderly patients (>65 years)AgeRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Metastatic renal cell carcinomaApproved by EMA; melanoma indication not universally approved across all EU member states.
• United StatesApprovedApproved: Metastatic renal cell carcinoma, Metastatic melanomaAldesleukin (Proleukin) approved by FDA; high-dose IV regimen.
• United KingdomApprovedApproved: Metastatic renal cell carcinomaMHRA approval maintained post-Brexit for renal cell carcinoma; usage largely supplanted by newer immunotherapies.

Aldesleukin (Proleukin), a recombinant form of human IL-2, is FDA-approved since 1992 for metastatic renal cell carcinoma and since 1998 for metastatic melanoma. Approved in multiple other jurisdictions. Various IL-2 variants and fusion proteins are in clinical development.

Evidence & Sources

No sources recorded yet.