Search

CN-121991224-A - Granulocyte-macrophage colony stimulating factor antibody and application thereof

CN121991224ACN 121991224 ACN121991224 ACN 121991224ACN-121991224-A

Abstract

The invention provides a granulocyte-macrophage colony stimulating factor antibody and application thereof, belonging to the technical field of biological medicine. Granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies or fragments have high affinity, are effective in blocking GM-CSF/GM-CSF receptor interactions, and are low in immunogenicity. The GM-CSF antibody or fragment can be used for preventing and/or treating diseases caused by human GM-CSF or detecting human GM-CSF protein or diagnosing related diseases caused by GM-CSF protein.

Inventors

  • SONG XINYU
  • NIU XUEFENG
  • LI SHIYUE
  • CHEN LING
  • ZHU YIPING
  • LIANG HUAN
  • MAO XIAOXIAO
  • HU FENHUA

Assignees

  • 广州医科大学附属第一医院（广州呼吸中心）
  • 广州呼吸健康研究院(广州呼吸疾病研究所)

Dates

Publication Date
20260508
Application Date
20260213

Claims (10)

  1. 1. The granulocyte-macrophage colony stimulating factor antibody or fragment is characterized by comprising a heavy chain variable region and/or a light chain variable region, wherein the amino acid sequence of CDR1 of the heavy chain variable region is shown as SEQ ID NO. 1, the amino acid sequence of CDR2 of the heavy chain variable region is shown as SEQ ID NO. 2, and the amino acid sequence of CDR3 of the heavy chain variable region is shown as SEQ ID NO. 3; The amino acid sequence of CDR1 of the light chain variable region is shown as SEQ ID NO. 4, the amino acid sequence of CDR2 of the light chain variable region is DVT, and the amino acid sequence of CDR3 of the light chain variable region is shown as SEQ ID NO. 5.
  2. 2. The granulocyte-macrophage colony stimulating factor antibody or fragment of claim 1, wherein the amino acid sequence of the heavy chain variable region is shown in SEQ ID No. 7 and the amino acid sequence of the light chain variable region is shown in SEQ ID No. 8.
  3. 3. The granulocyte-macrophage colony-stimulating factor antibody or fragment according to claim 1, further comprising at least one of a heavy chain constant region, a light chain constant region, an Fc region, and a flexible connecting peptide.
  4. 4. A nucleic acid molecule encoding the granulocyte-macrophage colony-stimulating factor antibody or fragment of any of claims 1-3.
  5. 5. A derivative material expressing the granulocyte-macrophage colony-stimulating factor antibody or fragment according to any one of claims 1-3, wherein the derivative material is selected from at least one of A1) to A7): A1 An expression cassette comprising the nucleic acid molecule of claim 4; a2 A recombinant vector comprising the nucleic acid molecule of claim 4; a3 A recombinant vector comprising the expression cassette of A1); a4 A recombinant microorganism or transgenic cell comprising the nucleic acid molecule of claim 4; a5 A recombinant microorganism or transgenic cell comprising the expression cassette of A1); A6 A) a recombinant microorganism or transgenic cell comprising the recombinant vector of A2); a7 A recombinant microorganism or transgenic cell containing the recombinant vector of A3).
  6. 6. Use of the granulocyte-macrophage colony-stimulating factor antibody or fragment according to any one of claims 1-3, the nucleic acid molecule according to claim 4 or the derivative material according to claim 5 for the preparation of a product for detecting human GM-CSF protein or for diagnosing a disease associated with GM-CSF protein or for the preparation of a medicament for preventing and/or treating a disease associated with human GM-CSF.
  7. 7. The use according to claim 6, wherein the disease caused by human GM-CSF comprises one of an inflammatory disease, an autoimmune disease and a cancer.
  8. 8. The use according to claim 7, wherein the autoimmune disease comprises at least one of autoimmune alveolar proteinosis, systemic autoimmune disease, systemic lupus erythematosus, rheumatoid arthritis, sjogren's syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, vasculitis, thyroid disease, type 1 diabetes, autoimmune hepatitis, multiple sclerosis, myasthenia gravis, autoimmune hemolytic anemia, immune thrombocytopenia, psoriasis, inflammatory bowel disease, and vitiligo.
  9. 9. A pharmaceutical composition comprising the granulocyte-macrophage colony-stimulating factor antibody or fragment of any of claims 1-3, the nucleic acid molecule of claim 4, or the derivative material of claim 5.
  10. 10. A test kit comprising the granulocyte-macrophage colony stimulating factor antibody or fragment of any one of claims 1-3 or expressed by the nucleic acid molecule of claim 4 or the derivative material of claim 5.

Description

Granulocyte-macrophage colony stimulating factor antibody and application thereof Technical Field The application belongs to the technical field of biological medicines, and particularly relates to a granulocyte-macrophage colony stimulating factor antibody and application thereof. Background Granulocyte-macrophage colony stimulating factor (Granulocyte-macrophage colony stimulating factor, GM-CSF), also known as colony stimulating factor 2 (CSF 2), is a monomeric glycoprotein secreted by a variety of cell types, such as macrophages, T cells, mast cells, NK cells, endothelial cells, fibroblasts, etc., belonging to a cytokine family member. GM-CSF is a key component of immune/inflammatory cascade, activates the cascade by binding to GM-CSF receptor, stimulates the differentiation and maturation of granulocytes and monocytes, and further activates a small amount of macrophages, which is critical for the body to resist infection. The pro-inflammatory properties of GM-CSF in turn make it a key causative agent of inflammatory and autoimmune diseases such as Rheumatoid Arthritis (RA), multiple Sclerosis (MS), crohn's disease, plaque psoriasis, asthma, etc., thus effectively blocking GM-CSF/GM-CSF receptor interactions is an important therapeutic strategy for such diseases and also represents a potential value in cancer treatment. GM-CSF targeted therapy has certain drawbacks, such as high cost of imported macromolecular drugs, and a heavy economic burden on patients. The anti-GM-CSF monoclonal antibody is an effective component for effectively blocking the binding of expected receptor of GM-CSF, and has the functions of diagnosis and prognosis detection. The currently reported anti-GM-CSF monoclonal antibodies are limited in the treatment and diagnosis of GM-CSF related diseases due to lack of high binding properties to human GM-CSF. Disclosure of Invention The invention aims to provide a granulocyte-macrophage colony stimulating factor antibody which has high binding affinity to human GM-CSF protein and has effective activity of inhibiting the binding of GM-CSF to its receptor. The invention provides a granulocyte-macrophage colony stimulating factor antibody or fragment, which comprises a heavy chain variable region and/or a light chain variable region, wherein the amino acid sequence of a CDR1 of the heavy chain variable region is shown as SEQ ID NO. 1, the amino acid sequence of a CDR2 of the heavy chain variable region is shown as SEQ ID NO. 2, and the amino acid sequence of a CDR3 of the heavy chain variable region is shown as SEQ ID NO. 3; The amino acid sequence of CDR1 of the light chain variable region is shown as SEQ ID NO. 4, the amino acid sequence of CDR2 of the light chain variable region is DVT, and the amino acid sequence of CDR3 of the light chain variable region is shown as SEQ ID NO. 5. Preferably, the amino acid sequence of the heavy chain variable region is shown as SEQ ID NO. 7, and the amino acid sequence of the light chain variable region is shown as SEQ ID NO. 8. Preferably, at least one of a heavy chain constant region, a light chain constant region, an Fc region, and a flexible connecting peptide is further included. The present invention provides a nucleic acid molecule encoding said granulocyte-macrophage colony-stimulating factor antibody or fragment. The present invention provides a derivative material expressing the granulocyte-macrophage colony-stimulating factor antibody or fragment, the derivative material being selected from at least one of A1) to A7): A1 An expression cassette comprising said nucleic acid molecule; a2 A recombinant vector comprising said nucleic acid molecule; a3 A recombinant vector comprising the expression cassette of A1); a4 A recombinant microorganism or transgenic cell containing said nucleic acid molecule; a5 A recombinant microorganism or transgenic cell comprising the expression cassette of A1); A6 A) a recombinant microorganism or transgenic cell comprising the recombinant vector of A2); a7 A recombinant microorganism or transgenic cell containing the recombinant vector of A3). The invention provides application of the granulocyte-macrophage colony-stimulating factor antibody or fragment, the nucleic acid molecule or the derivative material in preparing products for detecting human GM-CSF protein or diagnosing related diseases caused by the GM-CSF protein or preparing medicines for preventing and/or treating diseases caused by the human GM-CSF. Preferably, the disease caused by human GM-CSF includes one of inflammatory disease, autoimmune disease and cancer. Preferably, the autoimmune disease includes at least one of autoimmune alveolar proteinosis, systemic autoimmune disease, systemic lupus erythematosus, rheumatoid arthritis, sjogren's syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, vasculitis, thyroid disease, type 1 diabetes, autoimmune hepatitis, multiple sclerosis, myasthenia gravis, autoimmune hemolytic anemia, i