Modulating Cytokines as Treatment for Autoimmune Diseases and Cancer: Volume II

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Background

Cytokines are key mediators involved in the regulation of the normal immune response. Despite regulatory controls at multiple levels, abnormal immune responses involving cytokines may occur and cause various pathologies, including autoimmunity and cancer.

As deregulation of cytokine expression has a complex role in disease pathogenesis, novel therapeutic agents (e.g., anti-TNFa, anti-IL-17, anti-IL-12/23, IL-1RA) that neutralize cytokines have been successfully translated into clinical practice. For instance, the use of monoclonal anti-TNFa antibodies improved greatly the health of patients suffering from diseases like IBD, rheumatoid arthritis, spondyloarthritis, or psoriasis. Moreover, the use of effector cytokines (e.g., IL-2, IFNa, IL-15) either alone or in combination with other therapeutic reagents, such as the checkpoint inhibitors and the emergence of immunocytokines is accelerating in cancer immunotherapy. While, IL-2 has been approved by the Food and Drug Administration in 1992 for the treatment of metastatic kidney cancer and in 1998 for metastatic melanoma, researchers are still working on improving IL-2 efficacy and reducing toxicity. Fundamental discoveries on structural features of IL-2 in interaction with its different receptor chains led to the generation of IL-2 variants (eg. IL-2v, IL-2 “superkine”) that could selectively recruit the IL-2Rb/gc dimeric receptor over the IL-2Ra/IL-2Rb/gc trimeric receptor. Thus, these IL-2 variants represent promising tools for cancer therapy by activating T and NK effector cells, with minor effects on regulatory CD4 T cells. Additionally, given the broad range of biological activities of cytokines, the side effects of biologic therapies need to be carefully assessed and warrant the development of new therapeutics with more specificity of action.

In this research topic, we aim to provide a comprehensive overview of the array of innovative strategies employed to either enhance or inhibit cytokine functions from basic science to clinical applications. We welcome the submission of Reviews, Mini-Reviews and Original Research articles covering the following subtopics:

1. The development of reagents boosting cytokine action:
- Cytokine-derived agonists (muteins, fusion molecules).
- Cytokine / anti-cytokine mAb complexes to direct cytokine action.
- increasing cytokine’s half-life
- Immunocytokines, diabodies

2. The development of reagents inhibiting cytokine action or that thwart cytokine overexpression:
- Monoclonal antibodies or derivates targeting pro-inflammatory cytokines in inflammation or immunosuppressive cytokines in cancer.
- Cytokine-derived antagonists (muteins).
- Soluble receptors.
- Small chemical compounds or peptides inhibiting cytokine/receptor interaction.
- Small chemical compounds inhibiting cytokine pathways (JAK, STAT…).
- Multicytokines- versus selective-targeting.
- Other innovative new reagents.

This Research Topic is also open to novel strategies based on computational research to generate new reagents targeting cytokines, the new cytokines candidates to be targeted, and the related clinical applications.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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