Interleukin-15, human recombinant
Also known as: AMG 282, IL-15, Interleukin-15, N-803 (related superagonist), recombinant human interleukin‑15, rhIL-15
Source Interleukin-15, human recombinant at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
Human recombinant interleukin‑15 (IL‑15) is an investigational cytokine being explored primarily as an immune‑stimulating agent in cancer immunotherapy. It acts to expand and activate natural killer (NK) cells and CD8⁺ T cells, and is incorporated into a variety of experimental approaches, including direct protein infusion, engineered NK or CAR‑T cells, and oncolytic viruses.
Mechanism of Action
IL‑15 binds the heterotrimeric IL‑15 receptor complex composed of IL‑15Rα, IL‑2/15Rβ, and the common γ‑chain. This engagement triggers JAK1/3 activation and downstream STAT5 signaling, promoting survival, proliferation, and cytotoxic function of NK cells and memory‑phenotype CD8⁺ T cells. By sustaining expression of anti‑apoptotic proteins and enhancing metabolic fitness, IL‑15 supports long‑lasting immune effector responses without the activation‑induced cell death seen with IL‑2.
What the Research Shows
Recent reviews highlight IL‑15 as a central regulator of NK cell immunity and note multiple clinical trials testing IL‑15 or analogs in cancer (Ma et al., 2022). Pre‑clinical work demonstrated that brief pre‑activation with IL‑15 (alongside IL‑12 and IL‑18) creates memory‑like NK cells that produce more IFN‑γ and kill AML cells; a phase‑1 trial reported complete remissions in several patients (Romee et al., 2016). IL‑15 co‑expression in GPC3‑targeted CAR‑T cells increased in‑vivo expansion and yielded a 66 % disease‑control rate, though cytokine release syndrome (CRS) was more frequent (Steffin et al., 2024). An oncolytic herpesvirus (VG161) engineered to secrete IL‑15 (among other payloads) was well tolerated in a phase‑1 HCC study and reshaped the tumor microenvironment, suggesting synergistic antitumor activity (Shen et al., 2025). Across these studies, IL‑15 consistently augments innate and adaptive effector cells, but data remain early‑phase and largely limited to oncology.
Reported Benefits
Evidence indicates that IL‑15 can boost NK cell numbers, cytotoxicity, and cytokine production, leading to enhanced anti‑leukemia activity in memory‑like NK cell trials. When incorporated into CAR‑T cells, IL‑15 improves cell persistence, tumor infiltration, and objective response rates in solid‑tumor cohorts. The VG161 virus shows that IL‑15 delivery can remodel the tumor immune milieu and is tolerated without dose‑limiting toxicities. Collectively, IL‑15 offers a strategy to amplify cellular immunotherapies beyond what cytokine‑free approaches achieve.
Limitations of the Evidence
Most data are from early‑phase or pre‑clinical studies; long‑term efficacy and safety remain uncertain. The cytokine can provoke systemic inflammation, exemplified by increased CRS in IL‑15‑armed CAR‑T trials. Optimal dosing, route, and schedule for recombinant IL‑15 alone have not been established, and no regulatory approval exists for any indication. Comparative advantage versus other cytokines (e.g., IL‑2, IL‑7) has not been definitively shown.
Safety Considerations
IL‑15–driven immune activation can lead to cytokine release syndrome, fever, hypotension, and elevated inflammatory markers. In the IL‑15‑armed CAR‑T study, CRS was managed with IL‑1 or IL‑6 blockade and an inducible caspase‑9 safety switch. The VG161 oncolytic virus trial reported no dose‑limiting toxicities, suggesting that localized IL‑15 delivery may mitigate systemic effects. Nonetheless, comprehensive safety profiling is ongoing, and clinicians should monitor for signs of hyper‑inflammation during investigational use.
How It Is Administered
Recombinant IL‑15 is being investigated via continuous intravenous infusion, intermittent intravenous bolus, or subcutaneous injection. In cellular therapies, IL‑15 is delivered intracellularly by genetically engineered NK or CAR‑T cells, and in oncolytic virus platforms it is secreted by infected tumor cells. Formulations are protein‑based or encoded within viral vectors, and dosing regimens vary across trials.
Routes of Administration
Goals & Uses
- NK cell expansionImmunologyHigh
- Combination with checkpoint inhibitorsOncologyModerate
- CD8+ memory T cell homeostasisImmunologyHigh
- Enhance anti‑tumor immunityOncologyModerate
- HIV immunotherapy / viral reservoir reductionInfectious DiseaseLow
- Cancer immunotherapyOncologyModerate
- Boost antiviral responseInfectious DiseaseLow
Contraindications
- Severe cytokine release syndrome riskHematologicHigh
- Severe hepatic or renal impairmentOrgan ImpairmentModerate
- Organ transplant recipients on immunosuppressionTransplantHigh
- Active systemic infectionInfectiousHigh
- Active autoimmune diseaseAutoimmunityModerate
Adverse Effects
- Cytokine release syndromeImmunologicUncommonSystemic inflammatory response from immune activation
- Injection site reactionsLocalCommon
- ThrombocytopeniaHematologicCommonLow platelet count
- Cytokine release syndrome (CRS)ImmunologicalCommon
- HypotensionCardiovascularUncommonLow blood pressure
- Liver enzyme elevation (transaminitis)HepaticUncommon
- FatigueGeneralCommonLow energy or tiredness
- FeverSystemicCommonElevated body temperature
Drug Interactions
- Anti-PD-1/PD-L1 agents (e.g., pembrolizumab, nivolumab)Moderate
- Other pro-inflammatory cytokines (e.g., IL-2, IL-21)Moderate
- Immunosuppressive agents (e.g., cyclosporine, tacrolimus)High
- CyclosporineModerate
- CorticosteroidsModerate
Population Constraints
- Pediatric patientsAgeRelative
- Elderly patients (>75 years)AgeRelative
- Pregnant or lactating womenReproductiveRelative
- Patients with prior severe CRS or immunological toxicityMedical HistoryRelative
- Pregnant womenReproductiveAbsolute
Regulatory Status
- European UnionInvestigationalClinical trial authorization in multiple member states.
- United StatesInvestigationalIND holder; ongoing Phase I/II trials.
- United KingdomInvestigationalNo MHRA approval; investigated in clinical trials within academic frameworks.
Not approved for any indication; currently in Phase I/II clinical trials for solid tumors, hematologic malignancies, and viral infections.
Evidence & Sources
- Journal ArticleModerateMa S, Caligiuri MA, Yu J2022-01-01T00:00:00.000000Z
- Journal ArticleModerateInoue S, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateRomee R, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleModerateFrisoli ML, Essien K, Harris JE2020-01-01T00:00:00.000000Z
- Journal ArticleModerateShen Y, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleModerateSteffin D, et al.2025-01-01T00:00:00.000000Z
Frequently Asked Questions
What types of diseases are being targeted with IL‑15 research?
Current investigational work focuses on cancers, especially hematologic malignancies like acute myeloid leukemia and solid tumors such as hepatocellular carcinoma and GPC3‑expressing cancers. IL‑15 is used to boost NK or T‑cell activity in these settings.
How does IL‑15 differ from the more familiar cytokine IL‑2?
IL‑15 shares the common γ‑chain with IL‑2 but signals through a distinct receptor complex that favors proliferation and survival of NK and memory CD8⁺ T cells without inducing the activation‑induced cell death characteristic of IL‑2.
Can IL‑15 be given as a stand‑alone drug?
Recombinant IL‑15 can be administered alone by infusion or injection in early‑phase trials, but most clinical activity reported to date involves IL‑15 delivered via engineered cells or viruses that provide a sustained, localized source.
What are the main safety concerns for patients receiving IL‑15‑based therapies?
The principal risk is cytokine release syndrome, presenting with fever, hypotension, and organ dysfunction. In CAR‑T studies, CRS was managed with IL‑1/IL‑6 blockade and a built‑in safety switch. Ongoing trials continue to evaluate the frequency and severity of these events.
Is IL‑15 approved for any medical use?
No. IL‑15 remains an investigational agent; it has not received regulatory approval for any indication and is only available within clinical research protocols.
What is Interleukin-15, human recombinant?
Human recombinant interleukin‑15 (IL‑15) is an investigational cytokine being explored primarily as an immune‑stimulating agent in cancer immunotherapy. It acts to expand and activate natural killer (NK) cells and CD8⁺ T cells, and is incorporated into a variety of experimental approaches, including direct protein infusion, engineered NK or CAR‑T cells, and oncolytic viruses.
What is Interleukin-15, human recombinant used for?
Interleukin-15, human recombinant is educationally associated with: NK cell expansion, Combination with checkpoint inhibitors, CD8+ memory T cell homeostasis, Enhance anti‑tumor immunity, HIV immunotherapy / viral reservoir reduction, Cancer immunotherapy, Boost antiviral response. Educational only — not medical advice.
How is Interleukin-15, human recombinant administered?
Recorded routes of administration: Continuous Intravenous Infusion, Intravenous, Subcutaneous.
What are the potential side effects of Interleukin-15, human recombinant?
Reported adverse effects include: Cytokine release syndrome, Injection site reactions, Thrombocytopenia, Cytokine release syndrome (CRS), Hypotension, Liver enzyme elevation (transaminitis), Fatigue, Fever. This list is not exhaustive — consult a qualified clinician.
Who should avoid Interleukin-15, human recombinant?
Recorded contraindications: Severe cytokine release syndrome risk, Severe hepatic or renal impairment, Organ transplant recipients on immunosuppression, Active systemic infection, Active autoimmune disease. Consult a qualified clinician before use.