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CN-122011130-A - PD-1 and CTLA-4 double-target inhibition polypeptide or derivative thereof, pharmaceutically acceptable salt and application thereof

CN122011130ACN 122011130 ACN122011130 ACN 122011130ACN-122011130-A

Abstract

The application relates to the technical field of biological pharmacy, and in particular provides PD-1 and CTLA-4 double-target inhibition polypeptides or derivatives, pharmaceutically acceptable salts and application thereof, wherein the amino acid sequence of the polypeptides is shown as SEQ ID NO. 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be combined with PD-1 and CTLA-4 at the same time, can effectively block the combination between PD-1 and CTLA-4 and the ligand thereof, relieve the inhibition effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells, and remarkably enhance the immune response of organisms. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for detecting PD-1 and/or CTLA-4 and can also be used for treating or preventing related diseases caused by 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.
  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 thereof, a pharmaceutically acceptable salt or the 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

PD-1 and CTLA-4 double-target inhibition polypeptide or derivative thereof, pharmaceutically acceptable salt and application thereof Technical Field The application belongs to the technical field of biological pharmacy, and particularly relates to PD-1 and CTLA-4 double-target inhibition polypeptides or derivatives thereof, pharmaceutically acceptable salts and application thereof. Background The programmed death receptor-1 (PD-1) and the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are two important immune checkpoint proteins. PD-1 is predominantly expressed on the surface of activated T cells, and by binding to ligands expressed by tumor cells (PD-L1/PD-L2), intracellular ITSM motifs recruit protein tyrosine phosphatase SHP-2, resulting in dephosphorylation of TCR-related signaling molecules, attenuation of TCR signaling, leading to T cell function depletion, mediating immune escape of tumors. CTLA-4 then acts primarily in the early stages of the immune response (intra-lymph node), limiting the initial activation and proliferation of T cells by competing with CD28 for binding to B7 ligand. 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. There are also some studies on polypeptides targeting PD-1 or CTLA-4, but still further improvement is needed, and most focus on single targets, double-target polypeptides directed against PD-1 and CTLA-4 have not been reported. 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 combining affinity of the two targets and the stability of the molecules are difficult to be considered in the prior art. Therefore, the development of a novel PD-1 and CTLA-4 double-target inhibition polypeptide has important significance for clinical treatment. Disclosure of Invention The present application aims to solve at least one of the technical problems existing in the prior art to at least some extent. Therefore, the application provides a PD-1 and CTLA-4 double-target inhibition polypeptide or derivatives thereof, pharmaceutically acceptable salts and application thereof. In a first aspect of the application, the application provides a polypeptide or a derivative, pharmaceutically acceptable salt thereof. According to the embodiment of the application, the amino acid sequence of the polypeptide is shown as SEQ ID NO. 1. 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 effect of immune checkpoint proteins PD-1 and CTLA-4 on immune cells and obviously 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 application, the application provides a nucleic acid molecule. According to an embodiment of the application, 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 between the PD-1 and the CTLA-4 and the ligand thereof respectively, 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 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 third aspect of the application, the application provides an expression vector. According to an embodiment of the application, the expression vector carries the aforementioned nucleic acid molecule. Thus, the expression of the polypeptide or the derivative thereof and the pharmaceutically acceptable salt thereof can be effectively realized, and further, the in-vitro mass acquisition of the polypeptide or the derivative thereof and the pharmaceutically acceptable salt