Low toxicity interleukin-2 analogues for use in immunotherapy

Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin

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424 851, A61K 4505

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active

052291090

ABSTRACT:
The properties of two recombinant human IL-2 analogues with mutations at Arginine 38 (.fwdarw.Alanine) and Phenylalanine 42 (.fwdarw.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.

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