Low toxicity interleukin-2 analogues for use in immunotherapy

C - Chemistry – Metallurgy – 12 – N

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C12N 5/08 (2006.01) A61K 35/18 (2006.01) A61K 38/20 (2006.01) C07K 14/55 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2133831

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. secretions 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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