Human interleukin II mutant and application thereof

Abstract

The invention discloses a human interleukin II mutant and an application of the human interleukin II mutant in preparation of medicines. Mutation happens to a joint of an alpha acceptor and/or a beta acceptor and an amino acid sequence of human interleukin II protobiont, and the affinity of the human interleukin II to the alpha acceptor is reduced, thus the function of inducing regulatory T cells is reduced, the side effect that pulmonary edema can be caused can be reduced, the affinity to the beta acceptor is enhanced, and the attributes of the human interleukin II for natural killer cell immune activity are retained. The human interleukin II mutant can be used for stimulating an immune system and the function of inhibiting tumor growth is enhanced, thereby improving the clinical curative effect and application range.

Description

technical field [0001] The invention relates to a mutant of human interleukin II, in particular to a mutant of human interleukin II with low toxicity, high efficiency and little side effect and its use in the preparation of biomedicine. Background technique [0002] Interleukin II (interleukin-2, IL-2, interleukin II) is a lymphokine secreted by T lymphocytes (human interleukin II is a protein polypeptide chain composed of 133 amino acids, with a molecular weight of 15KD, and its amino acid sequence is as shown in the present invention Shown in the sequence listing SEQ ID No.1 and SEQ ID No.2), it is one of the most important molecules to maintain the normal function of the immune system. Interleukin II can promote the maturation of T cells, maintain the activity of T cells, and promote the activity of cytotoxic T lymphocytes, transform them into tumor infiltrating lymphocytes (TIL), promote the activity of natural killer (NK) cells, and induce killing Growth of tumor lymph...

AI Technical Summary

Problems solved by technology

[0005] However, at the same time, interleukin II has many toxic and side effects in clinic

At low doses, interleukin II promotes lymphocyte killing of tumors slightly, but it significantly promotes regulatory T cell function, increasing the number of peripheral blood regulatory T cells (T suppressor cells) (CD4+CD25+ cells) (JEM201:723-735), further inhibit the function and proliferation of infiltrating lymphocytes, and inhibit the anti-tumor immune response (JI26:85-93); at high doses, interleukin II can cause pain, high fever, nausea, Vomiting, pulmonary edema, vascular leakage, and even death (JCO21:3127-3132)

Due to its dual functions of killing tumor cells and promoting inhibitory cells, the clinical application of interleukin II is currently limited due to its severe toxicity. It is estimated that only about 20% of patients with related diseases can be treated with interleukin II

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