Polypeptide and use thereof
Provided are a polypeptide and nucleic acid for encoding the polypeptide, a nucleic-acid construct, an expression vector, and a host cell containing the nucleic acid, an antigen-presenting cell presenting the polypeptide on the surface of the cell, and immune effector cell thereof, a pharmaceutical composition containing the polypeptide, a vaccine containing the nucleic acid, the nucleic acid construct, the expression vector, the host cell, the antigen-presenting cell, and the immune effector cell, and an antibody recognizing the polypeptide. Also provided is a therapeutic method using the polypeptide, the nucleic acid, the pharmaceutical composition, the vaccine, and the antibody. Also provided are a diagnosis method and diagnosis apparatus for detecting the described polypeptide. Also provided is an application of the polypeptide in preparing a vaccine, a tumor diagnosis kit, or a pharmaceutical composition, and an application of the polypeptide or the nucleic acid as a test target in tumor diagnosis.
1. An isolated polypeptide consisting of 9 amino acids which has at least one of amino acid substitution with Methionine at position 2 and amino acid substitution with Leucine at position 9 in the amino acid sequence as depicted in SEQ ID NO: 1 (GLKDLLNPI), and the amino acids of the isolated polypeptide at positions 1 and 3-8 are same as that of SEQ ID NO: 1.
2. The isolated polypeptide according to claim 1 , wherein the isolated polypeptide is capable of binding with high affinity to HLA-A0201.
3. An isolated nucleic acid encoding the isolated polypeptide as defined in claim 1 , or a complement thereof.
4. A vaccine, comprising the isolated polypeptide of claim 1 as an active pharmaceutical ingredient, and a pharmaceutically acceptable adjuvant for use in the treatment of a tumor in a HLA-A0201 positive subject.
5. The vaccine of claim 4 , wherein the vaccine further comprises dendritic cells (DCs) that have been incubated with the isolated polypeptide.
6. A vaccine, comprising the isolated nucleic acid of claim 3 as an active pharmaceutical ingredient, and a carrier for use in the treatment of a tumor in a HLA-A0201 positive subject.
7. A method of treating a tumor associated with a mutation in PIK3CA gene in a HLA-A0201 positive subject in need thereof, the method comprises:
administering to the subject a therapeutically effective amount of the vaccine of claim 4 .
8. The method according to claim 7 , wherein the tumor is selected from breast cancer, lung cancer, nasopharyngeal carcinoma, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, skin cancer, prostate cancer, cervical cancer, leukemia and brain tumor.
9. A method of treating a tumor associated with a mutation in PIK3CA gene in a HLA-A0201 positive subject in need thereof, the method comprises:
administering to the subject a therapeutically effective amount of the vaccine of claim 6 .
10. The method according to claim 9 , wherein the tumor is selected from breast cancer, lung cancer, nasopharyngeal carcinoma, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, skin cancer, prostate cancer, cervical cancer, leukemia and brain tumor.
11. A diagnostic method, comprising:
detecting whether a biological sample derived from the subject contains the isolated polypeptide as defined in claim 1 , and
determining whether the subject suffers from a tumor based on the presence or absence of the polypeptide in the biological sample.
12. The method according to claim 11 , wherein the subject is an HLA-A0201 positive subject.
13. The method according to claim 12 , wherein the tumor is one or more selected from the group consisting of breast cancer, lung cancer, nasopharyngeal carcinoma, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, skin cancer, prostate cancer, cervical cancer, leukemia and brain tumor.
14. The isolated polypeptide according to claim 1 , wherein the isolated polypeptide has 9 amino acids as depicted in any one of SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4.