Interleukin-2 (IL-2) was one of the first cytokines discovered and its central role in T cell function soon led to the notion that the cytokine could specifically activate immune cells to combat cancer cells. Recombinant human IL-2 (recIL-2) belonged to the first anti-cancer immunotherapeutics that received marketing authorization and while it mediated anti-tumor effects in some cancer entities, treatment was associated with severe and systemic side effects. RecIL-2 holds an exceptional therapeutic potential, which can either lead to stimulation of the immune system - favorable during cancer treatment - or immunosuppression - used for treatment of inflammatory diseases such as autoimmunity. Due to these pleiotropic immune effects, recIL-2 therapy is still a hot topic in research and modified recIL-2 drug candidates show ameliorated efficacy and safety in pre-clinical and clinical studies. The Immune Safety Avatar (imSAVAR) consortium aims to systemically assess mechanisms leading to adverse events provoked by recIL-2 immunotherapy as a use case in order to aid safety evaluation of future recIL-2-based therapies. Here, we summarize the historical use of recIL-2 therapy, associated side effects, and describe the molecular basis of the dual role of IL-2. Finally, an overview of new recIL-2 compounds and delivery systems, which are currently being developed, will be given, highlighting a possible comeback of recIL-2 therapy.

09 Dec 2024·Journal of Immunotoxicology

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

Review

Author: Sewald, Katherina ; Dehmel, Susann ; Gogesch, Patricia ; Flandre, Thierry ; Sommer, Charline ; Neuhaus, Vanessa

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.

01 Apr 2024·Clinical Nuclear Medicine

Comparison of Lugano Criteria Versus RECIL and PERCIST as Prognostic Factors in Diffuse Large B-Cell Lymphoma

Article

Author: Jiang, Chong ; Tian, Rong ; Zhou, Yushan ; Su, Minggang ; Cui, Futao ; Tang, Pan

ObjectiveThis study aimed to compare the criteria of the Lugano, RECIL, and PERCIST for prognosis in patients with diffuse large B-cell lymphoma.Patients and MethodsWe retrospectively evaluated 335 patients with diffuse large B-cell lymphoma. All patients underwent baseline 18F-FDG PET/CT. Among them, 252 and 213 patients underwent interim PET/CT (I-PET/CT) and end-of-treatment PET/CT (EoT-PET/CT), respectively. Scans were interpreted by 2 nuclear medicine physicians using Lugano, RECIL, and PERCIST. RECIL and PERCIST were compared with Lugano for predicting progression-free survival (PFS) and overall survival (OS).ResultsAll 3 response criteria could be used to predict PFS and OS. In I-PET/CT, the concordance index of Lugano in predicting PFS and OS was higher than that of RECIL (both P = 0.043) or PERCIST (P = 0.008 and P = 0.034, respectively). In EoT-PET/CT, the concordance index of Lugano for predicting PFS and OS was similar to RECIL and not significantly different from PERCIST (P = 0.597 and P = 0.231, respectively).ConclusionsFor I-PET/CT, using the Lugano criteria is more accurate than RECIL or PERCIST in predicting PFS and OS. However, for EoT-PET/CT, the PERCIST criteria are minimally better.

100 Deals associated with Interleukin-2 biosimilar(Zenotech Laboratories Ltd.)

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Indication	Country/Location	Organization	Date
Renal Cell Carcinoma	IN	Zenotech Laboratories Ltd.	01 Mar 2008

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