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CN-122011132-A - Polypeptide or derivative thereof, pharmaceutically acceptable salt and application thereof

CN122011132ACN 122011132 ACN122011132 ACN 122011132ACN-122011132-A

Abstract

The invention relates to the technical field of biological pharmacy, and provides a polypeptide or a derivative, pharmaceutically acceptable salt and application thereof, wherein the amino acid sequence of the polypeptide is shown as SEQ ID NO. 1 or 2. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be combined with PD-1 and CTLA-4 simultaneously, so that the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells is relieved, the immune response of organisms is obviously enhanced, and the polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for treating or preventing related diseases caused by PD-1 and/or CTLA-4 and also can be used for detecting PD-1 and/or CTLA-4.

Inventors

  • HE BING
  • Lv Tianxu
  • YAO JIANHUA

Assignees

  • 腾讯科技（深圳）有限公司

Dates

Publication Date
20260512
Application Date
20260414

Claims (13)

  1. 1. A polypeptide or a derivative and pharmaceutically acceptable salt thereof is characterized in that the amino acid sequence of the polypeptide is shown as SEQ ID NO.1 or 2.
  2. 2. A nucleic acid molecule encoding the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof.
  3. 3. An expression vector comprising the nucleic acid molecule of claim 2.
  4. 4. A recombinant cell comprising the nucleic acid molecule of claim 2 or the expression vector of claim 3, or expressing the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof.
  5. 5. A conjugate comprising the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt, and a coupling moiety coupled thereto, wherein the coupling moiety is selected from a purification tag or label.
  6. 6. Use of the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3 or the recombinant cell of claim 4 in the preparation of a medicament which is an inhibitor of both PD-1 and CTLA-4 targets.
  7. 7. Use of the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3 or the recombinant cell of claim 4 in the manufacture of a medicament for the treatment or prevention of a disease associated with PD-1 and/or CTLA-4.
  8. 8. The use according to claim 7, wherein the PD-1 and/or CTLA-4 associated disease comprises a tumor or cancer.
  9. 9. The use of claim 8, wherein the tumor or cancer comprises a solid tumor or a hematological tumor.
  10. 10. Use of the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt thereof, or conjugate of claim 5 in the preparation of a reagent or kit for detecting PD-1 and/or CTLA-4.
  11. 11. A medicament comprising the polypeptide of claim 1 or a derivative thereof, a pharmaceutically acceptable salt thereof, the nucleic acid molecule of claim 2, the expression vector of claim 3, or the recombinant cell of claim 4.
  12. 12. A reagent or kit comprising the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt, or conjugate of claim 5.
  13. 13. A method of detecting PD-1 and/or CTLA-4, comprising: contacting a sample to be tested with the polypeptide of claim 1 or a derivative, pharmaceutically acceptable salt, conjugate of claim 5, or the reagent or kit of claim 12; determining whether PD-1 and/or CTLA-4 is contained in the sample to be tested based on the signal generated by the contacted product.

Description

Polypeptide or derivative thereof, pharmaceutically acceptable salt and application thereof Technical Field The invention belongs to the technical field of biological pharmacy, and particularly relates to a polypeptide or a derivative thereof, a pharmaceutically acceptable salt and application thereof. Background Programmed death receptor-1 (PD-1) is a key immune checkpoint receptor expressed primarily on the surface of activated T cells, B cells and bone marrow cells. In the physiological state, PD-1 transmits inhibitory signals by binding to ligands expressed by tumor cells (PD-L1 or PD-L2), inhibiting T cell overactivation, thereby maintaining immune tolerance and preventing autoimmune disease. However, in tumor microenvironments, tumor cells often "hijack" by a mechanism that highly expresses PD-L1, leading to the depletion of T cell function and mediating immune escape of the tumor. Thus, blocking the PD-1 pathway has become a core strategy for tumor immunotherapy, aimed at reactivating T-cell recognition and killing capacity of tumor cells. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is another transmembrane receptor that is predominantly expressed on the surface of activated T cells, belonging to the immunoglobulin superfamily, and is another key immunonegative regulatory molecule. CTLA-4 functions primarily in the early stages of the immune response (e.g., in the lymph nodes), limiting the initial activation and proliferation of T cells by competing with CD28 for binding to B7 ligand (CD 80/CD 86). CTLA-4 has important significance in regulating and controlling the intensity and breadth of anti-tumor immune response, and the inhibition aiming at the target spot can obviously enhance the immune response of organisms to tumors. Currently, the main clinical scheme aiming at PD-1 and CTLA-4 targets is monoclonal antibodies (Monoclonal Antibodies, mAbs), and the interaction between the monoclonal antibodies and corresponding ligands is blocked through high binding of PD-1 or CTLA-4, so that the inhibition of T cells is relieved, and the recognition and killing capacity of an immune system on tumor cells are restored. Blocking the PD-1 pathway alone often results in compensatory escape of the tumor by activating CTLA-4 or other immune checkpoints, resulting in insufficient therapeutic resistance or immune stimulation. In the field of polypeptide medicaments, the research on double-target peptides capable of simultaneously and accurately combining and blocking two targets of PD-1 and CTLA-4 is very few, and the design of the molecules requires very high spatial configuration accuracy and screening technology, so that the development of the technology for combining the binding affinity of the two targets and the stability of the molecules is relatively difficult. Therefore, a novel PD-1 and CTLA-4 double-target inhibition polypeptide is developed, and the polypeptide has important clinical value and application potential in the field of tumor immunotherapy. Disclosure of Invention The present invention aims to solve at least one of the technical problems existing in the prior art to at least some extent. For this purpose, the invention provides a polypeptide or its derivative, pharmaceutically acceptable salt and application thereof. In a first aspect of the invention, the invention provides a polypeptide or a derivative, pharmaceutically acceptable salt thereof. According to an embodiment of the invention, the amino acid sequence of the polypeptide is shown in SEQ ID NO. 1 or 2. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be combined with PD-1 and CTLA-4 simultaneously, and can block the combination between PD-1 and CTLA-4 and the ligand thereof respectively, relieve the inhibition of immune checkpoint inhibitor proteins PD-1 and CTLA-4 on immune cells, and remarkably enhance the immune response of organisms, thereby realizing the treatment of related diseases caused by PD-1 and/or CTLA-4. In addition, the polypeptide or the derivative thereof and the pharmaceutically acceptable salt thereof can be used for qualitatively and/or quantitatively detecting PD-1 and/or CTLA-4. In a second aspect of the invention, the invention provides a nucleic acid molecule. According to an embodiment of the invention, the nucleic acid molecule encodes a polypeptide as described previously or a derivative, pharmaceutically acceptable salt thereof. The polypeptide or the derivative and the pharmaceutically acceptable salt of the polypeptide coded by the nucleic acid molecule can be combined with PD-1 and CTLA-4 simultaneously, and simultaneously blocks the combination of the PD-1 and the CTLA-4 and the ligand thereof, so that the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells is relieved, the immune response of an organism is obviously enhanced, and the treatment of related diseases caused by PD-1 and/or CTLA-4 is realized. In addition, the po