Comparing the functionality of proleukin (R) and akron interleukin-2 through an analysis of key T cell subsets

Background \u0026 Aim Recombinant human interleukin-2 (IL-2) promotes the proliferation of activated T cells and has long been used in vivo to stimulate and maintain the growth of effector T cells and increasingly, to expand T cells in vitro for adoptive cell therapy in patients with cancer. IL-2 was approved by the FDA for treatment of metastatic renal cancer in 1992 and for treatment of metastatic melanoma in 1998. However, its administration in the approved dose has been associated with potentially fatal side effects, including vascular toxicity. There have recently been efforts to improve upon the existing product, marketed as Proleukin® (aldesleukin), through modifications to the molecule, through the development of fusion proteins, and through the development of low-dose formulations. Akron Biotechnology manufactures IL-2 for in vitro use. The product is embedded in several clinical and commercial CAR T therapies. Moreover, the company has sought to register a novel, low-dose formulation of its IL-2 to treat patients suffering from acute and chronic graft versus host disease (GVHD) . The data confirms the functional similarity of Proleukin® and Akron\u0027s IL-2, bolstering the product\u0027s utility for both in vitro and in vivo uses. Methods, Results \u0026 Conclusion Methods CyTOF: antibody panel designed by Dana Farber Cancer Institute. There are three categories of target proteins: surface proteins,intracellular markers and signaling molecules. Different markers were checked after stimulation with Akron IL-2 or Proleukin® (15 minutes) and verified with lymphocyte subset and intrinsic signaling cascade. Results The research focused on three major T cell subset populations (Treg, Tcon and CD8 T cells).Upon stimulation with Akron IL-2 and Proleukin®, CD25, CD122, CD132, CTLA-4, PD-1,PD-L1 markers were checked for T cell subsets, observed via t-SNE plot. The data indicated that the antibody panel setting was accurate and reliable; each marker was expressed in the expected T cell subset. For example: CD25 was expressed exclusively in Tregs. The expression of pSTAT5, pSTAT3, and pSTAT1 was identical in Akron IL-2 and Proleukin®, controlling for exposure and dosage . These results confirm that Akron IL-2 and Proleukin® are identical in their ability to boost adaptive immune response. Conclusions This study demonstrates that Akron\u0027s IL-2 is functionally similar to Proleukin®, its utility for adoptive immunotherapies, and potentially for treatment of patients suffering from autoimmune diseases.