, 2011 and Koreth et al., 2011). Further clinical trials with suitable dose ranges in various autoimmune indications may prove beneficial as evidence suggests that striking the balance between the types of cells (e.g., Tregs, T effector cells etc) that are induced by IL-2 will be needed for effective immunotherapy with IL-2 (Malek and Pugliese, 2011). Based on this premise, trials in diabetic patients and future directions for use

of IL-2 therapy are currently being considered (http: //clinicaltrials.gov/ct2/show/NCT01353833; Long et al., 2013). Vorinostat mouse The 1st WHO International Standard (IS) for Interleukin-2 (IL-2) (86/504) consisting of a highly purified preparation of glycosylated IL-2 derived from Jurkat cells (Robb et al., 1983) was established by the WHO Expert Committee on Biological Standardisation (ECBS) in 1987. On the basis of an international collaborative study involving a wide range of bioassays which predominantly used either mouse or human T cell-lines and, in rare instances, lectin-stimulated blast cells, the WHO 1st IS for IL-2 (coded 86/504) see more was assigned a potency of 100 IU/ampoule (WHO Expert Committee on Biological Standardisation, 1988 and Gearing and Thorpe, 1988).

To date, the 1st IS for IL-2 has proved suitable for its intended purpose, in particular, potency labelling of approved IL-2 products including Proleukin (INN Aldesleukin) the first clinical product. Since stocks of the 1st IS are, however, nearly exhausted, the WHO ECBS in 2011 recognized the need for a replacement international

standard for IL-2 and agreed that lyophilized candidate preparations from the previous collaborative study (for establishment of 1st IS) for IL-2 should be evaluated in a study and, subject to their suitability, be considered to serve as a potential replacement standard. The 1st IS for IL-2 was selected based on prevailing opinion (over 20 years ago) that a T cell derived material may be advantageous. However, this has not been borne out by experience gained over the last two decades and given that T cell derived material is no longer produced and marketed products are E. coli Non-specific serine/threonine protein kinase expressed, it is appropriate that the standard is prepared using E. coli expressed material. Furthermore, it has been shown that glycosylation of IL-2 does not affect its biological activity (Robb et al., 1984 and Koichi, 1988). On the basis of this rationale, we evaluated in a multi-centre international collaborative study, two candidate IL-2 preparations, both expressed in E. coli, with the main objective of selecting and characterizing a suitable WHO 2nd IS (for replacement for the 1st IS) for the bioassay of human IL-2 and assigning a unitage of IL-2 activity.