Type 2 responses determine skin rash during recombinant interleukin-2 therapy
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...
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2343359 |
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| author | Charline Sommer Vanessa Neuhaus Patricia Gogesch Thierry Flandre Susann Dehmel Katherina Sewald |
| author_facet | Charline Sommer Vanessa Neuhaus Patricia Gogesch Thierry Flandre Susann Dehmel Katherina Sewald |
| author_sort | Charline Sommer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d7da3c4f6c9e4169b6cac7a4e73a7e96 |
| institution | Kabale University |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-d7da3c4f6c9e4169b6cac7a4e73a7e962024-12-10T10:30:20ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012024-12-0121sup1S48S5910.1080/1547691X.2024.2343359Type 2 responses determine skin rash during recombinant interleukin-2 therapyCharline Sommer0Vanessa Neuhaus1Patricia Gogesch2Thierry Flandre3Susann Dehmel4Katherina Sewald5Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department for Preclinical Pharmacology and Toxicology, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hanover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department for Preclinical Pharmacology and Toxicology, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hanover, GermanyDivision of Immunology, Paul-Ehrlich-Institut, Langen, GermanyNovartis AG, Basel, SwitzerlandFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department for Preclinical Pharmacology and Toxicology, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hanover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department for Preclinical Pharmacology and Toxicology, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hanover, GermanyThe 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.https://www.tandfonline.com/doi/10.1080/1547691X.2024.2343359ImmunotherapyIL-2 therapycutaneous adverse drug reactionstype 2 immunityadverse outcome pathwayimSAVAR |
| spellingShingle | Charline Sommer Vanessa Neuhaus Patricia Gogesch Thierry Flandre Susann Dehmel Katherina Sewald Type 2 responses determine skin rash during recombinant interleukin-2 therapy Journal of Immunotoxicology Immunotherapy IL-2 therapy cutaneous adverse drug reactions type 2 immunity adverse outcome pathway imSAVAR |
| title | Type 2 responses determine skin rash during recombinant interleukin-2 therapy |
| title_full | Type 2 responses determine skin rash during recombinant interleukin-2 therapy |
| title_fullStr | Type 2 responses determine skin rash during recombinant interleukin-2 therapy |
| title_full_unstemmed | Type 2 responses determine skin rash during recombinant interleukin-2 therapy |
| title_short | Type 2 responses determine skin rash during recombinant interleukin-2 therapy |
| title_sort | type 2 responses determine skin rash during recombinant interleukin 2 therapy |
| topic | Immunotherapy IL-2 therapy cutaneous adverse drug reactions type 2 immunity adverse outcome pathway imSAVAR |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2343359 |
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