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Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide

A technology of epitope peptides and nuclear cells, which is applied in the direction of antineoplastic drugs, peptides, and drug combinations, and can solve problems such as small molecular weight, peptides are easily degraded by peptidases, and poor immunogenicity

Active Publication Date: 2015-01-07
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The biggest weakness of a single polypeptide vaccine is its poor immunogenicity, the polypeptide is easily degraded by peptidases in the body, and the induced CTL is not easy to break through the threshold required for tumor regression
For example, although the WT1 epitope peptide vaccine has achieved initial success in clinical trials, current researchers often use peptides with a single CTL epitope, which are small in molecular weight and easily degraded by proteolytic enzymes, so they can only stimulate low-level immune responses. Combining multiple CTL epitopes, increasing Th epitopes, using immune adjuvants, constructing multi-epitope peptides and fusion peptides can improve the immunogenicity of polypeptides

Method used

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  • Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide
  • Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide
  • Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide

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Embodiment Construction

[0039] The present invention will be further described in detail below in conjunction with specific examples, which are explanations of the present invention rather than limitations.

[0040] The present invention provides an acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, which is CP701 CTL epitope peptide nonapeptide, and its amino acid sequence is 236 ILDRHNFAI 244 (As shown in SEQ.ID.NO.1), the molecular weight is 1098.8Da.

[0041] The invention provides a novel anti-acute monocytic leukemia polypeptide vaccine, provides the preparation method of the polypeptide vaccine, and confirms the anti-acute monocytic leukemia curative effect of the polypeptide vaccine through animal experiments. The composition of the peptide vaccine is MLAA-34 CP701 polypeptide (50 μg) + universal T helper cell epitope (T) (tetanus endotoxin) (50 μg) + incomplete Freund's adjuvant (IFA) (1 mL ).

[0042] Among them, the acute monocytic leukemia antigen MLAA-34 CP701 CT...

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Abstract

The invention discloses an acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide and an application of the acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and belongs to the technical field of biology. The acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide disclosed by the invention can induce specific CTL, and simultaneously can express tumor cells of MLAA-34 and HLA-A*0201, and T2 cells of loaded peptide in vitro to generate the determined specific killing effect; the epitope polypeptide CP701 is applied to preparation of a polypeptide vaccine aiming at acute monocytic leukemia; and the polypeptide vaccine composed of an MLAA-34 epitope peptide CP701 (236ILDRHNFAI244), a T auxiliary epitope and an incomplete Freund adjuvant can inhibit hu-PBL-SCID amplification of tumors in mice loading human monocytic leukemia cells THP-1, prolongs the survival life, and can induce the specific CTL killing activity and NK cytotoxic activity in vivo.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to an acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide and its vaccine and pharmaceutical application. Background technique [0002] Acute myeloid leukemia (AML) has a poor prognosis, especially those with adverse chromosomal or molecular abnormalities, mainly due to the high relapse rate after chemotherapy-induced remission. The eradication of minimal residual disease (MRD) after remission remains a huge challenge. Allogeneic hematopoietic stem cell transplantation (hematopoietic stem cell transplantation, HSCT) shows effective anti-leukemia effect, but because of the difficulty of matching, high cost, and more importantly, some life-threatening complications, such as graft-versus-host disease ( graft versus host disease, GVHD), only suitable for a small number of young and suitable patients. Therefore, there is an urgent need to develop new therape...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K7/08A61K38/10A61P35/02A61K38/08
Inventor 白菊何爱丽张王刚王剑利杨云贺军涛
Owner XI AN JIAOTONG UNIV
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