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Monitoring and diagnosis for immunotherapy, and design for therapeutic agent

A device, sequencing technology, applied in the determination/inspection of microorganisms, for the analysis of 2D or 3D molecular structure, bioreactors/fermenters for specific purposes, etc., can solve the problem of cancer that has not been fully studied targeting mutant gene products Immunotherapy and other issues

Pending Publication Date: 2018-12-21
REPERTOIRE GENESIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Meanwhile, specific cancer immunotherapy targeting mutated gene products (neoantigens) has not been sufficiently studied (Non-Patent Document 1)

Method used

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  • Monitoring and diagnosis for immunotherapy, and design for therapeutic agent
  • Monitoring and diagnosis for immunotherapy, and design for therapeutic agent
  • Monitoring and diagnosis for immunotherapy, and design for therapeutic agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0197] (Example 1: Sorting of mutant peptides and detection of immunogenicity - against tumors in human subjects)

[0198] (analyze)

[0199] based on figure 2 Mutant peptides were sorted using the protocol exemplified in .

[0200] Specifically, do the following.

[0201] (1) Subjects of the following groups were used.

[0202] Target patient: 65-year-old Japanese male lung cancer patient

[0203] Prior to performing the Examples, the following HLA types were identified by typing using the Luminex assay.

[0204] HLA type: HLA-A*02:01,24:02

[0205] (2) Extract DNA from normal tissue and tumor tissue. Exome sequencing was performed with the HiSeq 2000 sequencer from Illumina using the TruSeq PE kit. The equipment used was a sequencer HiSeq 2000 from Illumina, and the software used was the control software of the same sequencer.

[0206] (Exome Read Mapping)

[0207] Next, bwa was used with the following parameters to map exome reads from normal and tumor tissues res...

Embodiment 2

[0318] (Example 2: Sorting of mutant peptides and detection of immunogenicity - for mice)

[0319] In this example, the same experiment can be performed when using mice.

[0320] Its procedure is as follows.

[0321] 1. Neoantigens can be searched for spontaneously, chemically and radiation-induced tumors (cancer, sarcoma or leukemia) in all syngenic mouse strains. In this example, a mouse strain was used: C57BL / 6 (MHC haplotype H2 b ). Tumors: B16 melanoma cells were used as tumors.

[0322] 2. Collect tissue from the cancer site of the cancer-bearing mouse, and collect the same organ / tissue as the tumor site in the normal mouse, wherein the tumor site and the non-tumor site (for example, tumor of colon cancer) are collected in the cancer-bearing mouse sites and non-tumor sites). Normal tissues were collected from normal mice when the mice were from the same strain.

[0323] 3. Extract DNA and RNA from collected tissues / organs for exome-seq and RNA-seq analysis.

[032...

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PUM

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Abstract

The present invention provides a method for producing a peptide for the treatment (in particular, immunotherapy), monitoring, or diagnosis of a disease in a subject. This method is achieved by obtaining information pertaining to a genome read, for example an exome read, of the subject and a mutation thereof, and, as necessary, information regarding the RNA sequence of the subject and information regarding the MHC type of the subject, analyzing an epitope related to the mutation on the basis of the information pertaining to the genome read (for example, the exome read) and the mutation, arbitrary information from the RNA sequence, the MHC type information, and information regarding the disease, and producing a peptide, as necessary, on the basis of information regarding the epitope.

Description

technical field [0001] The present invention relates to the design of diagnostic, monitoring and therapeutic agents for immunotherapy. More specifically, the present invention relates to analyzing epitopes based on information about the genome (eg, exome) and mRNA, MHC-based information, and other biological information to design peptides useful for immunotherapy based on the results thereof. Background technique [0002] Recent developments in medicine and biology, especially the rapid development of next-generation sequencing (NGS), have made genome-wide analysis of cancer cells relatively easy and enabled the analysis of genetic changes associated with cellular oncogenic transitions at the individual level. Through such developments, individualized therapy using molecularly targeted therapeutics to modulate the function of mutated genes has become common in the field of clinical medicine. Meanwhile, specific cancer immunotherapy targeting mutated gene products (neoantige...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/09C07K7/04C12M1/00C12Q1/6886G01N33/48G06F19/16G16B15/00
CPCG01N33/574G01N33/6878C12Q1/6881C12Q2600/156G16B50/10G16B20/20G16B15/00C07K7/04G16B40/00G16B20/30G16B5/20G16B15/30G16B25/10G16B30/10G16B50/20G16B5/00G16B45/00G16B20/00G16B30/00
Inventor 新井理铃木隆二
Owner REPERTOIRE GENESIS
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