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Revival of recombinant IL-2 therapy–approaches from the past until today

Roser, Luise A. ; Sommer, Charline ; Ortega Iannazzo, Samira ; Sakellariou, Christina LU orcid ; Waibler, Zoe and Gogesch, Patricia (2024) In Journal of Immunotoxicology 21(sup1). p.38-47
Abstract

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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immune safety, Immune-related adverse event, immunotherapy, imSAVAR, interleukin-2, new recombinant IL-2 compounds
in
Journal of Immunotoxicology
volume
21
issue
sup1
pages
38 - 47
publisher
Informa Healthcare
external identifiers
  • scopus:85211935273
  • pmid:39655498
ISSN
1547-691X
DOI
10.1080/1547691X.2024.2335219
language
English
LU publication?
yes
id
04f76fb7-3cf5-46df-ac26-7b1de1d6ec07
date added to LUP
2025-01-27 12:42:30
date last changed
2025-07-15 01:52:53
@article{04f76fb7-3cf5-46df-ac26-7b1de1d6ec07,
  abstract     = {{<p>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.</p>}},
  author       = {{Roser, Luise A. and Sommer, Charline and Ortega Iannazzo, Samira and Sakellariou, Christina and Waibler, Zoe and Gogesch, Patricia}},
  issn         = {{1547-691X}},
  keywords     = {{immune safety; Immune-related adverse event; immunotherapy; imSAVAR; interleukin-2; new recombinant IL-2 compounds}},
  language     = {{eng}},
  number       = {{sup1}},
  pages        = {{38--47}},
  publisher    = {{Informa Healthcare}},
  series       = {{Journal of Immunotoxicology}},
  title        = {{Revival of recombinant IL-2 therapy–approaches from the past until today}},
  url          = {{http://dx.doi.org/10.1080/1547691X.2024.2335219}},
  doi          = {{10.1080/1547691X.2024.2335219}},
  volume       = {{21}},
  year         = {{2024}},
}