Oncolytic virus and neoantigen combined tumor vaccine and preparation method thereof

A technology of oncolytic virus and tumor vaccine, which is applied in the field of genetic engineering to achieve the effect of improving efficiency and enhancing anti-cancer efficacy

Active Publication Date: 2019-11-12
HANGZHOU NEOANTIGEN THERAPEUTICS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In order to solve the deficiencies in the prior art, the object of the present invention is to provide a tumor vaccine combined with oncolytic virus and neoantigen and its preparation method. The combined vaccine can be realized in two ways. The first is to use oncolytic The tumor killing of viral reagents produces a local immune response in tumor lesions, improves the phagocytosis efficiency of neoantigen polypeptide vaccines by antigen-presenting cells, and the number of T cells that can specifically recognize tumor neoantigens and tumor infiltration ability

Method used

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  • Oncolytic virus and neoantigen combined tumor vaccine and preparation method thereof
  • Oncolytic virus and neoantigen combined tumor vaccine and preparation method thereof
  • Oncolytic virus and neoantigen combined tumor vaccine and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0048] Embodiment one: sample construction and preparation;

[0049] It mainly includes 4 sample construction and preparation, and the preparation process includes the following contents:

[0050] 1. Identification and preparation of neoantigen polypeptides

[0051] 1.1 Identification of individualized tumor neoantigen polypeptide sites

[0052] The DNA sequencing results of normal cells of C57BL6 mice / tumor patients and the DNA sequencing results of 6 sequencing samples of B16F10 cells / patient tumor cells and inoculated tumors / patient tumors were compared to the mouse / human reference genome from A somatic mutation in the tumor cells is identified in the comparison;

[0053] RNA sequencing was then performed on the three sequencing samples to identify and assess the expression of the mutated allele;

[0054] Predict the type I and type II HLA types of C57BL6 mice / clinical patients based on the genome comparison results, and use the affinity prediction algorithm netMHCpan to...

Embodiment 2

[0079] Example 2: Evaluating the drug efficacy of the combination of oncolytic virus and neoantigen polypeptide vaccine with a mouse-derived pharmacodynamic model;

[0080] 1. Construction of mouse tumor model——C57-B16F10 melanoma model;

[0081] Select C57BL / 6 mice, purchased from Beijing Weitong Lihua, female, 6-8 weeks old. B16-F10 murine melanoma tumor cells were inoculated. Tumor cells were counted before inoculation to ensure that the cell viability was above 95%. The harvested B16-F10 melanoma cells were divided into 7×10 4 cells / Subcutaneous injection in the back only.

[0082] 2. Evaluation of anti-tumor effect

[0083] 2.1 Tumor model grouping;

[0084] Two days after the tumor formation of the mice, 50-60 mice with similar tumor volume and an average tumor diameter of about 0.5 cm were selected and randomly divided into four groups with at least 10 mice in each group, which were the negative control adjuvant group , polypeptide group, oncolytic virus group, po...

Embodiment 3

[0105] Example 3: Drug efficacy evaluation of the combination of oncolytic virus and neoantigen polypeptide vaccine on the humanized drug efficacy model;

[0106] 1. Human-derived tumor model construction

[0107] 1.1 Immune reconstitution humanized PDX mouse model construction - Humanized NOD / SCID mouse PDX model

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Abstract

The invention discloses an oncolytic virus and neoantigen combined tumor vaccine and a preparation method thereof. The combined vaccine can be implemented through the following two ways: in the firstway, an immune response reaction generated from an oncolytic virus reagent is used for improving the efficiency for phagocytizing a polypeptide reagent by an antigen presenting cell, increasing the number of T cells which can specifically identify a neoantigen and improving the tumor invasion performance of the T cells so as to enhance the anti-cancer curative effect; and in the second way, a genecoding a tumor neoantigen is inserted into an oncolytic virus vector to massively express the tumor neoantigen, and is combined with the tumor killing performance of the oncolytic virus to further enhance the immune response reaction of a tumor focus local part and improve the invasion degree of the killing type T cell in a tumor tissue, so that the local part can generate an immune response reaction, and generation of an effector cell is stimulated to achieve an anti-cancer effect. Experiment comparison discovers that the first combined vaccine and the second combined vaccine have an excellent tumor inhibition effect, and the second combined vaccine has a remarkable tumor inhibition effect.

Description

technical field [0001] The invention relates to the field of genetic engineering, in particular to a tumor vaccine combined with an oncolytic virus and a neoantigen and a preparation method thereof. Background technique [0002] For a long time, finding effective ways to attack tumors has been the goal pursued by researchers. One of the biggest difficulties lies in the widespread heterogeneity of tumors. Not only within the tumor tissue, even within the same tumor type, there are great differences among different patients. During the rapid growth and proliferation of cancer cells, it is often too late to repair the errors that occur during DNA replication, so many new mutant proteins will appear, which are called neoantigens (Neoantigen). Early studies believed that the mutations carried by most tumor neoantigens had no effect on the growth of tumor cells and were negligible by-products. With the deepening of research, scientists have recently discovered that even if the m...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K48/00A61P35/00C12N15/861A61K35/76
CPCA61K39/0011A61K48/0025A61K48/005A61K35/76A61P35/00C12N15/86A61K2039/5256C12N2710/10343A61K2300/00
Inventor 莫凡刘亮韩宁陈荣昌
Owner HANGZHOU NEOANTIGEN THERAPEUTICS CO LTD
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