Aldesleukin 18million unit powder for solution for injection vials

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, including impaired regulatory T cell (Treg) function. Low-dose interleukin-2 (Ld-IL-2) therapy has emerged as a promising approach to selectively expand Tregs and restore immune tolerance in SLE. This systematic review evaluates current evidence on the efficacy and safety of Ld-IL-2 therapy in patients with SLE. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, the Cochrane Library, and the Virtual Health Library for studies published up to April 10, 2025. Eligible studies included randomized controlled trials, cohort studies, and open-label trials that investigated Ld-IL-2 therapy in adult patients with SLE. Data were extracted on study design, patient demographics, intervention details, clinical and immunologic outcomes, adverse events, and predictive biomarkers. Risk of bias was assessed using the Modified Downs and Black checklist. Seven studies met the inclusion criteria, encompassing a total of 517 patients with active SLE. All studies reported significant expansion of Treg populations following Ld-IL-2 treatment. Clinical outcomes consistently showed reductions in disease activity scores, such as SLEDAI and BILAG, with SRI-4 response rates ranging from 43% to 65.5%. Ld-IL-2 therapy was well tolerated, with adverse events primarily limited to mild injection-site reactions and flu-like symptoms. No serious treatment-related infections or concerns about immunogenicity were observed. Several studies identified baseline biomarkers, including low complement C3 levels, elevated PD-1^hi^ Tregs, and reduced CD4+ T cell counts, as predictors of treatment response. Ld-IL-2 therapy appears to be a safe and effective immunomodulatory treatment for patients with SLE, capable of enhancing Treg function and reducing disease activity. While current evidence is encouraging, larger multicenter randomized trials are warranted to establish standardized treatment protocols and validate predictive biomarkers for optimized patient selection.

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BackgroundPatients undergoing gastrointestinal cancer surgery are often immunocompromised and susceptible to infectious complications. Recombinant Interleukin 2 activates effector immune cells and stimulates the expansion of regulatory T-cells, making it a promising intervention for prevention of inflammatory complications.ObjectiveOur objective was to investigate effects of different preoperative rIL2 dosages on postoperative outcome parameters.MethodsWe conducted a systematic literature review and meta-analysis and included RCTs that recruited adult patients undergoing gastrointestinal cancer surgery who received preoperative subcutaneous rIL2. We performed a systematic search of MEDLINE (via PubMed), Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) from 1989 up to April 18th, 2024.ResultsOut of 2324 screened studies, we included 13 RCTs with a total of 504 patients. Lymphocyte counts [cells/mm3] at 1 week postoperative were higher in the intervention compared to the control group (MD 865 (95%CI: 26, 1705)). Surgical site infections and systemic infections were less likely to occur in the intervention group (OR 0.13 (95%CI: 0.03, 0.50); OR 0.25 (95%CI: 0.10, 0.66)). Severe side effects of rIL2 were not reported.ConclusionPreoperative rIL2-based immunomodulation prevents postoperative immunosuppression while the occurrence of severe side effects does not seem to be relevant.

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Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as "cures". Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998.

Abstract licence: CC BY 4.0

We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs. IL-2R-expressing cells, (b) avoiding any FcγR-binding and Fc effector functions and (c) reduced binding to endothelial cells expressing CD25; and (iii) improve the pharmacokinetics, and thus convenience of administration, of IL-2. The crystal structure of the IL2v-IL-2Rβγ complex was determined and CEA-IL2v activity was assessed using human immune effector cells. Tumor targeting was investigated in tumor-bearing mice using 89Zr-labeled CEA-IL2v. Efficacy studies were performed in (a) syngeneic mouse models as monotherapy and combined with anti-PD-L1, and in (b) xenograft mouse models in combination with ADCC-mediating antibodies. CEA-IL2v binds to CEA with pM avidity but not to CD25, and consequently did not preferentially activate Tregs. In vivo, CEA-IL2v demonstrated superior pharmacokinetics and tumor targeting compared with a wild-type IL-2-based CEA immunocytokine (CEA-IL2wt). CEA-IL2v strongly expanded NK and CD8+ T cells, skewing the CD8+:CD4+ ratio toward CD8+ T cells both in the periphery and in the tumor, and mediated single agent efficacy in syngeneic MC38-CEA and PancO2-CEA models. Combination with trastuzumab, cetuximab and imgatuzumab, all of human IgG1 isotype, resulted in superior efficacy compared with the monotherapies alone. Combined with anti-PD-L1, CEA-IL2v mediated superior efficacy over the respective monotherapies, and over the combination with an untargeted control immunocytokine. These preclinical data support the ongoing clinical investigation of the cergutuzumab amunaleukin immunocytokine with abolished CD25 binding for the treatment of CEA-positive solid tumors in combination with PD-L1 checkpoint blockade and ADCC competent antibodies.

Abstract licence: CC BY-NC-ND 4.0

IntroductionInflammation plays a critical role in the pathogenesis of atherosclerosis, the leading cause of ischaemic heart disease (IHD). Studies in preclinical models have demonstrated that an increase in regulatory T cells (Tregs), which have a potent immune modulatory action, led to a regression of atherosclerosis. The Low-dose InterLeukin 2 (IL-2) in patients with stable ischaemic heart disease and Acute Coronary Syndromes (LILACS) study, established the safety of low-dose IL-2 and its biological efficacy in IHD. The IVORY trial is designed to assess the effects of low-dose IL-2 on vascular inflammation in patients with acute coronary syndromes (ACS).Methods and analysisIn this study, we hypothesise that low-dose IL-2 will reduce vascular inflammation in patients presenting with ACS. This is a double-blind, randomised, placebo-controlled, phase II clinical trial. Patients will be recruited across two centres, a district general hospital and a tertiary cardiac centre in Cambridge, UK. Sixty patients with ACS (unstable angina, non-ST elevation myocardial infarction or ST elevation myocardial infarction) with high-sensitivity C reactive protein (hsCRP) levels >2 mg/L will be randomised to receive either 1.5×106 IU of low-dose IL-2 or placebo (1:1). Dosing will commence within 14 days of admission. Dosing will comprise of an induction and a maintenance phase. 2-Deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) scans will be performed before and after dosing. The primary endpoint is the change in mean maximum target to background ratios (TBRmax) in the index vessel between baseline and follow-up scans. Changes in circulating T-cell subsets will be measured as secondary endpoints of the study. The safety and tolerability of extended dosing with low-dose IL-2 in patients with ACS will be evaluated throughout the study.Ethics and disseminationThe Health Research Authority and Health and Care Research Wales, UK (19/YH/0171), approved the study. Written informed consent is required to participate in the trial. The results will be reported through peer-reviewed journals and conference presentations.Trial registration numberNCT04241601.

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