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A7.06 Low-dose IL-2 therapy in refractory sle: Insights from a phase I/IIA clinical trial
  1. JY Humrich1,3,4,
  2. C von Spee-Mayer1,
  3. E Siegert1,
  4. M Bertolo1,
  5. D Abdirama1,
  6. A Rose1,
  7. P Enghard2,
  8. A Radbruch3,
  9. GR Burmester1,
  10. G Riemekasten4
  1. 1Department of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany
  2. 2Department of Nephrology and Intensive Care Medicine, Charité – University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
  3. 3German Rheumatism Research Center (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany
  4. 4Department of Rheumatology, University Hospital Schleswig-Holstein - Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Abstract

Interleukin-2 (IL-2) is crucial for the growth and survival of regulatory T cells (Treg), and thus for the control of autoimmunity. In previous studies we have proven the significance of an acquired IL-2 deficiency and related Treg defects in the pathogenesis of systemic lupus erythematosus (SLE). Accordingly, we showed that compensation of IL-2 deficiency by IL-2 therapy corrects associated Treg defects and ameliorates already established disease in lupus-prone mice.1 Proceeding to a clinical translation of IL-2 therapy for SLE, we recently reported a rapid and robust reduction of disease activity in parallel to a remarkable expansion of the Treg population by low-dose IL-2 therapy in one patient with refractory SLE.2 In addition, we showed that Treg defects in SLE patients are associated with IL-2 deficiency, and can be selectively corrected in vitro and in vivo with low doses of IL-2.3 Together, these studies provided the rationales for the clinical implementation an IL-2-based immunotherapy for the treatment of SLE with the aim to restore Treg activity and thus to re-establish endogenous mechanisms of immune tolerance.

Here, we present results from the ongoing phase I/IIa clinical trial (PRO-IMMUN) addressing the safety, tolerability, immunological responses and clinical efficacy of a subcutaneous low-dose IL-2 therapy in patients with refractory SLE.

References

  1. Humrich JY, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA. 2007;107(1):204–209

  2. Humrich JY, et al. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015. doi: 10.1136/annrheumdis-2014-206506

  3. von Spee-Mayer C, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. Aug 31 2015. doi: 10.1136/annrheumdis-2015-207776. [Epub ahead of print]

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