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Novel antigen peptide composition and application thereof in tumor immunotherapy drugs

A technology of immunotherapeutic drugs and antigenic peptides, which is applied in the fields of molecular immunology and biomedicine, and can solve problems such as low accuracy of neoantigens, unsatisfactory immunogens, and damage to normal tissue cells

Pending Publication Date: 2020-12-29
天津亨佳生物科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current cancer vaccines can contain both shared tumor-associated antigens and neoantigens based on mutations in tumor genes, where associated antigens are natural proteins that are selectively expressed or overexpressed in tumors found in many individuals, but due to their susceptibility to The immunosuppressive effect of self-tolerance is not ideal as an immunogen for targeting T-cell responses against specific tumor types; neoantigen vaccines can overcome some of the shortcomings of vaccines containing shared tumor Ideal target for therapy, as neoantigens are only expressed specifically in tumors, so are less likely to induce tolerance and damage normal tissue cells
However, the use of patient-specific neoantigens requires sequencing the genome and HLA typing of individual subjects and calculating the individualized neoantigen peptide composition that may be applicable to the individual subject, making the designed vaccine applicable to very limited populations , and the accuracy of the calculated neoantigens is generally not very high, and its immunogenicity still needs further evaluation

Method used

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  • Novel antigen peptide composition and application thereof in tumor immunotherapy drugs
  • Novel antigen peptide composition and application thereof in tumor immunotherapy drugs
  • Novel antigen peptide composition and application thereof in tumor immunotherapy drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 New Antigen Peptide Immune Function Verification

[0050] 1. Isolation of Peripheral Blood Mononuclear Cells (PBMCs)

[0051] Take 20ml of venous blood from a healthy donor with the corresponding HLA type, dilute the blood sample with an equal volume of sterile PBS, transfer the lymphocyte separation solution (Stemcell, 07861) into a new 50ml centrifuge tube, and ensure that the blood volume ratio is 3 : 4. Carefully add the diluted blood to the surface of the separation liquid, operate as gently as possible, avoid mixing, and clearly see the boundary between the two liquids. Centrifuge at 400g for 30min at room temperature. After centrifugation, suck out the mononuclear cell layer, transfer it to a new sterile centrifuge tube, and add PBS to wash twice. Cells were resuspended in RPMI-1640 medium and counted.

[0052] 2. Enzyme-linked immunospot (ELISPOT) verification of peptide immune response

[0053] Will 2.5×10 6 Each cell was suspended in 90% RPMI-16...

Embodiment 2

[0057] Example 2 Neoantigen peptide activates specific T lymphocytes

[0058] 1. Isolation and induction of DC cells

[0059] T cells and monocytes were isolated from PBMCs of healthy donors typed HLA-A1101, and monocytes were first enriched using a human CD14 positive selection kit (STEMCELL, 18058). T cells were then isolated from CD14- cells using a human T cell isolation kit (STEMCELL, 17951). Monocytes were suspended in X-VIVO-15 medium and adjusted to 1 × 10 6 / mL, and then treated with GM-CSF (100ng / mL) and IL-4 (50ng / mL). Incubate cells at 37 °C, 5% CO 2 cultured for 6 days to induce immature DC, and then TNF-α (10ng / mL), IL-1β (10ng / mL), IL-6 (100ng / mL), LPS (1μg / mL) and PGE2 (1μg / mL) for 24 hours to induce DC maturation.

[0060] 2. Induction of specific cytotoxic T lymphocytes (CTLs) by DCs loaded with neoantigen peptide compositions

[0061] Will 2.5×10 5 DC cells with 1×10 6 T cells were mixed, and IL-2 (50ng / mL), IL-7 (5ng / mL), IL-15 (10ng / mL) and the ne...

Embodiment 3

[0064] Example 3 In vivo anti-tumor experiment of specific T lymphocytes activated by neoantigen peptide composition

[0065] Take the A1101-H2172 cells in the logarithmic growth phase, the cell density is about 80-90%, digest the cells with trypsin, wash twice with pre-cooled PBS, and adjust the cells to an appropriate concentration. Take 20 6-week-old nude mice, weighing 18-20g, and subcutaneously inoculate 1×10 7 Cells were observed to form tumors, and nude mice with a tumor diameter of 5 mm were selected and randomly divided into two groups. The treatment group was given the CTL cells prepared in Example 2, and injected 1×10 7 cells / time, 2 times a week for 3 consecutive weeks. The control group was given PBS solution. The tumor size was measured every week, the tumor volume was calculated, and the survival rate of the two groups was observed. The result is as figure 2 As shown, compared with the control group, the tumor survival rate of the CTL cell treatment group ...

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Abstract

The invention provides a novel antigen peptide composition and application thereof in tumor immunotherapy drugs. The novel antigen peptide composition comprises at least one novel antigen peptide in SEQ ID No. 1-26; the tumor immunotherapy drugs are immunogenic compositions or vaccine compositions for immunotherapy of tumor patients, and comprise at least one novel antigen peptide in SEQ ID No. 1-26 and pharmaceutically acceptable auxiliary materials; the novel antigen peptide composition can be used for treating patients with tumor cells containing corresponding gene mutation and HLA typing of at least one novel antigen peptide in SEQ ID No. 1-26. Novel antigen epitopes in the novel antigen peptide composition are verified by immunogenicity, and have the effect of activating T cells to kill tumor cells in a targeted manner; the novel antigen peptide composition can be used for preparing drugs for treating EGFR mutant tumor patients, is wider in treatment range, and provides a new choice for immunotherapy of patients.

Description

technical field [0001] The invention belongs to the technical fields of molecular immunology and biomedicine, and specifically relates to a neoantigen peptide composition and its application in tumor immunotherapy drugs. Background technique [0002] Lung cancer is a common and highly malignant tumor in clinical practice, with a very poor prognosis, and the five-year survival rate is less than 10%. According to histological classification, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer, and the incidence of non-small cell lung cancer accounts for about 80%. Surgery is the first choice and main treatment method for lung cancer. However, more than half of non-small cell lung cancer patients have already developed distant metastases when they were first diagnosed, and lost the opportunity for surgical treatment. The emergence of tumor-targeted drugs has greatly changed the traditional treatment model of tumors, greatly improved the progn...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/71A61P39/00A61P35/00
CPCA61P35/00A61K39/001104C07K14/71
Inventor 杜发明李凤娥霍冲邓丽刚邹庆薇王亚玲
Owner 天津亨佳生物科技发展有限公司
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