Design, preparation and application of novel IL-2, INF alpha and Fc fusion protein

Abstract

According to the invention, modifications aiming at human interleukin-2 (IL-2) and interferon alpha (IFN alpha) are included; the fusion protein is formed by IL-2, INF alpha or IL-2 / INF alpha double factors and Fc after modification; as well as the design, preparation and use of these fusion proteins; respectively fusing the mutant IL-2 and the mutant INF alpha (double factors) at the N terminal or the C terminal of the Fc; fusing the mutant IL-2 at the N terminal or the C terminal of the Fc; respectively fusing the mutant INF alpha at the N end or the C end of the Fc; l234A / L235A mutation is introduced into the Fc segment at the same time, so that the binding capacity of the Fc segment and a receptor FcgRIII is reduced; m252Y / S254T / T256E mutation is introduced, so that the half-life period of the protein is prolonged; through gene mutation, the binding capacity of IL-2 and a receptor thereof and the binding capacity of INFalpha and a receptor thereof are changed, mutants better than wild type mutants are obtained, the binding capacity with NK cells and CD8 + T cell receptors is improved, and the defects that existing drugs are weak in specificity and large in side effect are overcome.

Description

Technical field [0001] The invention is a biomedical technology field, which involves the design, preparation and use of the new IL-2 and INFα and FC fusion proteins. Background technique [0002] IL-2, also known as T cell growth factor, is the gene is located in No. 4 chromosomes, including a sequence of 7KB, consisting of 133 amino acids, and the molecular weight is about 15kd. IL-2 acts through IL-2R. IL-2R includes three subunit, IL-2Rα (ie CD25), IL-2Rβ (ie CD122), and IL-2R γ (ie CD132). Three sub-submissions can form three forms of receptor: high binding force receptor contains all three sub-meter IL-2Rα / β / β / β, and the binding force receptor contains IL-2Rβ / γ two sub-macro Receptor IL-2Rα. Among them, IL-2Rβ and IL-2R γ are necessary for IL-2 to activate the downstream signal pathway. When IL-2 is combined with IL-2Rβ and IL-2Rγ at the same time, the two receptor subunit forms a heterogeneous diode, phosphorylationization The STAT5 in the cells enters the corresponding ge...

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Problems solved by technology

[0005] In order to solve the above problems, the present invention discloses the design, preparation and application of a novel fusion protein of IL-2, INFα and Fc. Through gene mutation, the binding ability of IL-2 and its receptor, INFα and its receptor can be changed to solve the current problem. It has the disadvantages of weak drug specificity, short half-life and large side effects

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