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Key Publications

March 13, 2023

Biased IL-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate long-term lung allograft acceptance in mice

Transplantation of solid organs can be life-saving in patients with end-stage organ failure, however, graft rejection remains a major challenge. In this study, by pre-conditioning with interleukin-2 (IL-2)/anti-IL-2 antibody complex treatment biased toward IL-2 receptor α, we achieved acceptance of fully mismatched orthotopic lung allografts that remained morphologically and functionally intact for more than 90 days in immunocompetent mice.
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December 16, 2020


Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species


Stimulation of regulatory T (Treg) cells holds great promise for the treatment of autoimmune, chronic inflammatory, and certain metabolic diseases. We developed anti-human interleukin-2 (IL-2) monoclonal antibodies, which we screened using a cell-based and dynamic IL-2 receptor (IL-2R) platform, leading in the identification of UFKA-20. Binding of UFKA-20 to human IL-2 resulted in IL-2/UFKA-20 complexes that preferentially activated Treg cells in mice and nonhuman primates in vivo and in primary human immune cells ex vivo. These results pave the way to development of IL-2/UFKA-20 complexes for use in clinical trials.
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November 10, 2015


Interleukin-2: Biology, Design and Application


Interleukin-2 (IL-2) exerts crucial functions during immune homeostasis via its effects on regulatory T (Treg) cells, and the optimizing and fine-tuning of effector lymphocyte responses. Thus, somewhat paradoxically, low doses of recombinant IL-2 have been used for Treg cell-based immunosuppressive strategies against immune pathologies, while high-dose IL-2 has shown some success in stimulating anti-tumor immune responses.
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February 17, 2012


The role of interleukin-2 during homeostasis and activation of the immune system


Stimulation with IL-2 is crucial for the maintenance of regulatory T (Treg) cells and for the differentiation of CD4+ T cells into defined effector T cell subsets following antigen-mediated activation. For CD8+ T cells, IL-2 signals optimize both effector T cell generation and differentiation into memory cells. Use of IL-2 — either alone or in complex with particular neutralizing IL-2-specific antibodies — can amplify CD8+ T cell responses or induce the expansion of the Treg cell population, thus favoring either immune stimulation or suppression.
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March 31, 2006


Selective stimulation of T cell subsets with antibody-cytokine immune complexes


Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. When coupled with recombinant IL-2, some IL-2/IL-2 mAbcomplexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ Tregs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.
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