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AL

aldesleukin (Recil)

✓ Approved

Zenotech · IL2RA · Recombinant Proteins

What is aldesleukin?

aldesleukin is a recombinant proteins developed by Zenotech. It is approved for therapeutic indications via injectable (others).

Drug Profile

Brand NamesRecil
CompanyZenotech
Drug ClassRecombinant Proteins
Molecular TargetIL2RA
RouteInjectable (Others)
StatusApproved
Sources: ClinicalTrials.gov, Zenotech

Mechanism of Action

Molecular Targets

aldesleukin acts on 1 molecular target:

IL2RAinterleukin 2 receptor subunit alpha (IL2R, TCGFR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

aldesleukin is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Renal cancer✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Skin cancer✓ Approved

Related Research Articles

PubMedSkin appendage disorders2025-12-18

Immune Cell-Targeting Biologics for Alopecia Areata: A New Paradigm in Precision Medicine.

Gaumond Simonetta I SI, Opstal Madisyn M, Kamholtz Isabella I, Jimenez Joaquin J JJ

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with limited treatment options for severe disease. Although Janus kinase inhibitors have recently been approved, safety concerns remain, highlighting the need for alternative targeted therapies. Biologics that modulate immune cell activity may offer novel therapeutic avenues in AA. A review of peer-reviewed case reports, case series, and clinical trials evaluating immune cell-targeting biologics for AA, including rituximab, abatacept, alefacept, efalizumab, nivolumab, aldesleukin. Rituximab (anti-CD20) achieved complete remission in 1 patient with alopecia universalis. Abatacept (CTLA4-Ig) reduced mean SALT score by 71% in responders, though no response occurred in patients with extensive disease. Alefacept (anti-CD2 fusion) showed no significant improvement over placebo in a clinical trial, yet case reports documented up to 100% regrowth. Efalizumab (anti-CD11a) failed to improve SALT in a phase II trial, but individual cases achieved 70-100% regrowth. Nivolumab (PD-1 inhibitor) produced complete regrowth maintained beyond 1 year in a single case. Aldesleukin (low-dose IL-2) did not yield statistically significant efficacy in a clinical trial; however, a pilot study reported all patients experiencing hair regrowth along with improvements in quality of life. Across studies, adverse events were mild, with no serious events reported. (1) Biologics targeting B and T cells demonstrated moderate efficacy overall, suggesting that B-cell depletion and T-cell modulation may be viable strategies in AA, although better targets are needed to improve efficacy. (2) Abatacept showed partial regrowth in multiple patients, while alefacept, efalizumab, and aldesleukin were largely ineffective in controlled trials, despite several case-level responses. (3) Rituximab and nivolumab achieved complete regrowth in isolated cases, but evidence remains anecdotal.

PMID 41409530
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PubMedEuropean journal of nuclear medicine and molecular imaging2025-07-01

[68Ga]Ga-interleukin-2 for imaging activated T-lymphocytes: biochemical characterization and phase I study in normal subjects.

Signore Alberto A, Galli Filippo F, Varani Michela M, Campagna Giuseppe G et al.

This study aimed to develop a ready-to-use kit for 68Ga-labelling of interleukin-2 (IL2) facilitating PET imaging of activated T-lymphocytes. Human recombinant IL2 (hrIL2) and Aldesleukin (desIL2), conjugated with two different chelators (NODAGA and THP) were compared. Conjugated-IL2 was stored, freeze-dried at -80 °C and radiolabelled at room temperature. In vitro quality controls (iTLC, HPLC, SDS-PAGE, spectrometry and binding assays on activated T-lymphocytes) and in vivo biodistribution studies in BALB/c mice, were performed. The shelf life of the lyophilized kits was assessed up to 6 months of storage, by iTLC, HPLC and SDS-PAGE. First-in-human study was conducted in 5 volunteers by performing [68Ga]Ga-THP-desIL2 PET/CT acquisitions at several time-points, to assess biodistribution and dosimetry. Mass spectrometry showed that only one molecule of THP or NODAGA is bound to N-terminus of both IL2 proteins. The most efficient conjugation was observed for THP-desIL2. [68Ga]Ga-THP-desIL2 showed higher labelling yield (LY) (59.13 ± 2.58%), radiochemical purity (RCP) (97.91 ± 0.45%) and binding affinity to its receptor on activated T-cells (Kd = 0.584 nM/L) and a more favorable biodistribution in pre-clinical studies, with rapid kidney metabolism and lower liver uptake than [68Ga]Ga-NODAGA-desIL2 and [68Ga]Ga-THP-hrIL2. Lyophilized kit of THP-desIL2 remained stable at -80 °C up to 6 months maintaining high RCP and LY. Phase I study showed a rapid plasma clearance, renal metabolism, safety and favorable dosimetry. We developed an efficient lyophilized kit of THP-desIL2 for 68Ga-labelling at room temperature in GMP conditions, obtaining excellent in vitro and in vivo results. [68Ga]Ga-THP-desIL2 PET/CT studies in humans showed favorable dosimetry and safety, thus highlighting its potential for a wide range of clinical applications, particularly in immune-mediated diseases and cancer.

PMID 40590904
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PubMedThe Lancet. Oncology2025-05-03

Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial.

Lou Emil E, Choudhry Modassir S MS, Starr Timothy K TK, Folsom Timothy D TD et al.

Over the past decade, immunotherapeutic strategies-mainly targeting the PD-1-PD-L1 immune checkpoint axis-have altered cancer treatment for many solid tumours, but few patients with gastrointestinal forms of cancer have benefited to date. There remains an urgent need to extend immunotherapy efficacy to more patients while addressing resistance to current immune checkpoint inhibitors. The aim of this study was to determine the safety and anti-tumour activity of knockout of CISH, which encodes cytokine-inducible SH2-containing protein, a novel intracellular immune checkpoint target and a founding member of the SOCS family of E3-ligases, using tumour infiltrating lymphocyte (TILs) genetically edited with CRISPR-Cas9 in patients with metastatic gastrointestinal epithelial cancers. For this first-in-human, single-centre, phase 1 trial, patients aged 18-70 years with a diagnosis of metastatic gastrointestinal epithelial cancer with progressive disease following at least one first line standard therapy, measurable disease with at least one lesion identified as resectable for TIL generation and at least one other lesion meeting RECIST criteria as measurable to serve as an indicator of disease response, and an ECOG performance status of 0 or 1 were screened and enrolled if meeting these and all other eligibility criteria. TILs procured from tumour biopsies were expanded on the basis of neoantigen reactivity, subjected to CRISPR-Cas9-mediated CISH knockout, and infused intravenously into 12 patients after non-myeloablative lymphocyte depleting chemotherapy (cyclophosphamide 60 mg/kg per dose on study days -6 and -5, and fludarabine 25 mg/m2 per dose on days -7 to -3) followed by high-dose IL-2 (aldesleukin; 720 000 IU/kg per dose). The primary endpoint was safety of administration of neoantigen-reactive TILs with knockout of the CISH gene, and a key secondary endpoint was anti-tumour activity measured as objective radiographic response and progression-free and overall survival. This study is registered with ClinicalTrials.gov, NCT04426669, and is complete. Between May 12, 2020, and Sept 16, 2022, 22 participants were enrolled in the trial (one patient was enrolled twice owing to lack of TIL outgrowth on the first attempt); ten patients were female, and 11 were male (self-defined). One patient was Asian, the remainder were White (self-defined). We successfully manufactured CISH knockout TIL products for 19 (86%) of the patients, of whom 12 (63%) received autologous CISH knockout TIL infusion. The median follow-up time for the study was 129 days (IQR 15-283). All 12 (100%) patients had treatment-related severe adverse events. The most common grade 3-4 adverse events included haematological events (12 patients [100%]) attributable to the preparative lymphodepleting chemotherapy regimen or expected effects of IL-2, fatigue (four patients [33%]), and anorexia (three patients [25%]). Deaths of any cause for patients on study were attributed to the underlying disease under study (metastatic gastrointestinal cancer) and related complications (10 patients) or infection (grade 5 septicaemia in one patient). There were no severe (≥grade 3) cytokine release or neurotoxicity events. Six (50%) of 12 patients had stable disease by day 28, and four (33%) had stable disease ongoing at 56 days. One young adult patient with microsatellite-instability-high colorectal cancer refractory to anti-PD1/CTLA-4 therapies had a complete and ongoing response (>21 months). These results support the safety and potential antitumour activity of inhibiting the immune checkpoint CISH through the administration of neoantigen-reactive CISH-knockout TILs, with implications for patients with advanced metastatic cancers refractory to checkpoint inhibitor immunotherapies, and provide the first evidence that a novel intracellular checkpoint can be targeted with therapeutic effect. Intima Bioscience.

PMID 40315882
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PubMedPloS one2025-02-06

Drug-induced autoimmune-like hepatitis: A disproportionality analysis based on the FAERS database.

Ye Wangyu W, Ding Yuan Y, Li Meng M, Tian Zhihua Z et al.

Drug-induced autoimmune-like hepatitis (DI-ALH) is a potentially life-threatening condition that can lead to acute liver failure and necessitate liver transplantation. While the association between certain drugs and DI-ALH has been documented, a comprehensive analysis of drug-related signals in a large, real-world pharmacovigilance database is lacking. This study aimed to systematically identify drugs linked to DI-ALH by analyzing adverse event reports from the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) database. We searched the FAERS database for the term "autoimmune hepatitis" and extracted DI-ALH reports from the first quarter of 2004 to the first quarter of 2024. Positive signal drugs were identified using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). To confirm a significant drug-adverse event association, each method had to meet predefined thresholds: for PRR and ROR, values were considered significant if the lower 95% confidence interval (CI) was greater than 1 and at least three reports were identified; for BCPNN, an Information Component (IC025) greater than 0 indicated a signal; for EBGM, a value greater than 2 for the lower 95% confidence interval (EBGM05) was used to denote a positive signal. A total of 5,723 DI-ALH reports were extracted from the FAERS database. Disproportionality analysis identified 50 drugs with strong associations to DI-ALH, with biologics, statins, antibiotics, and antiviral drugs representing the most common categories. Among these, nitrofurantoin (ROR 94.79, CI 78.53-114.41), minocycline (ROR 77.82, CI 65.09-93.05), and nivolumab (ROR 47.12, CI 15.06-147.39) exhibited the strongest signals. Additionally, several previously unreported drugs, including mesalazine, aldesleukin, onasemnogene abeparvovec-xioi, and nefazodone, were identified as having strong associations with DI-ALH. These findings were consistent across all four signal detection methods, further validating the robustness of the associations. This study provides a comprehensive assessment of drugs associated with DI-ALH through a rigorous analysis of the FAERS database using multiple signal detection methods. By identifying both well-known and previously underreported drugs, this study contributes to a more complete understanding of drug-induced liver injury. The findings have important implications for pharmacovigilance strategies and clinical risk assessment. However, limitations inherent in the FAERS database, such as underreporting and the potential for reporting bias, should be considered. Further clinical validation is warranted to confirm these associations.

PMID 39913410
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PubMedJournal for immunotherapy of cancer2025-01-22

Art of TIL immunotherapy: SITC's perspective on demystifying a complex treatment.

Turcotte Simon S, Donia Marco M, Gastman Brian B, Besser Michal M et al.

In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment of patients with metastatic melanoma. The infusion of autologous tumor-infiltrating T lymphocytes (TIL) is capable of mediating durable tumor regression and is now Food and Drug Administration-approved for patients with disease refractory to immune checkpoint inhibitors. Since the advent of chimeric antigen receptor (CAR) T cells for patients with hematological malignancies, a growing network of centers capable of delivering effector T cell products to patients has developed. Administration of TIL can be layered onto that institutional framework, but there are many complex and unique aspects to TIL immunotherapy. The highly multidisciplinary clinical expertise and coordination required to successfully and safely deliver TIL to patients began within the National Cancer Institute Surgery Branch and have been subsequently adopted worldwide. The general steps, most of which require hospital inpatient resources, include a surgical procedure to harvest sufficient tumor for TIL manufacturing, admission for non-myeloablative lymphodepleting chemotherapy followed by TIL, and intravenous interleukin-2 (IL-2, aldesleukin). Here, we provide the principles, practice, and required resources underlying the efficient and safe delivery of TIL immunotherapy derived from the clinical expertise of high-volume centers around the world. This article enhances published clinical practice guidelines by providing underlying clinical rationale and data-driven examples to demystify TIL immunotherapy in order to facilitate uptake and improve patient access to this promising treatment modality in clinical and research settings.

PMID 39837618
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PubMedJournal of immunotoxicology2024-12-10

Type 2 responses determine skin rash during recombinant interleukin-2 therapy.

Sommer Charline C, Neuhaus Vanessa V, Gogesch Patricia P, Flandre Thierry T et al.

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy. Skin rashes and other side effects, together with poor efficacy led to a drawback of the therapeutic, but modified recIL-2 molecules are on the rise to treat both cancer and inflammatory diseases such as autoimmunity. Still, pathophysiological mechanisms of recIL-2-induced skin rashes are not understood. In the study reported here, a hypothetical literature-based immune-related adverse outcome pathway (irAOP) was developed to identify possible key cells and molecules in recIL-2-induced skin rash. Using this approach, a hypothesis was formed that the induced immune response predominantly is Type 2-driven by T-helper and innate lymphoid cells, leading to the occurrence of cutaneous side effects during recIL-2 therapy. This paper further discusses mechanisms beyond the proposed irAOP which might add to the pathology but currently are less-studied. Together, this hypothetic irAOP forms a basis to clarify possible cellular and molecular interactions leading to recIL-2-induced skin rash. This might be used to adapt existing or develop new test systems to help predict and prevent cutaneous side effects in future IL-2-based or similar therapies.

PMID 39655497
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