Low toxicity interleukin-2 analogues for use in immunotherapy

摘要

The properties of two recombinant human IL-2 analogues with mutations at Arginine 38 (->Alanine) and Phenylalanine 42 (->Lysine) were analyzed and compared to those of native IL-2. These analogues were found to maintain their ability to bind to the intermediate IL-2 receptor, p75, while binding only minimally to the high affinity p55+p75 receptor complex. The analogues also maintained the ability to stimulate peripheral blood mononuclear cells to generate lymphokine activated killing (LAK). However, IL-1 beta and TNF- alpha secretion were significantly reduced in response to the analogues, as compared to the native IL-2 molecule. These analogues are therefore potentially valuable low-toxicity alternatives to IL-2 in human immunotherapy and adoptive immunotherapy treatment strategies.