Supercharge Your Innovation With Domain-Expert AI Agents!

A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (MSI) cancers

A cancer vaccine and microsatellite technology, applied in the direction of tumor-specific antigens, tumor rejection antigen precursors, cancer antigen components, etc., can solve high-risk problems

Active Publication Date: 2020-06-23
NOUSCOM AG
View PDF16 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In particular, individuals with heterozygous germline mutations in the MSH2 or MLH1 genes of the MMR pathway (approximately 90% of inherited LS carriers) are at increased risk for cancer

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (MSI) cancers
  • A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (MSI) cancers
  • A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (MSI) cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0097] In a first aspect, the present invention relates to a method of selecting a collection of frameshift peptides (CFSP) to generate a general microsatellite instability (MSI) cancer vaccine peptide collection (CVP) for the prevention or treatment of patients with cancer or patients at risk of developing such cancers, including hereditary and sporadic MSI cancers, the method includes the following steps:

[0098] (i) a collection of selected nucleic acids (CFSM), each nucleic acid comprising a frameshift mutation (FSM), each FSM present in one or more than one of at least M cancer samples (CS), each cancer sample all patients are different, wherein the patient's cancer includes cancer cells with an MSI phenotype;

[0099] Where at least 50% of the selected FSMs meet criteria (a), (b), (c) and / or (d):

[0100] (a) FSM is present in a single nucleotide repeat (MNR) of a coding gene equal to or greater than 6 nucleotides in length;

[0101] (b) FSM corresponds to a deletion ...

Embodiment 1

[0319] Example 1: Selection of single nucleotide repeat (MNR) mutations in protein-coding genes from MSI tumor samples

[0320] Mutation Annotation Format (MAF) files are based on complete exome sequence data (published 4.0-October 31, 2016) and are available from the TCGA Data Portal ( https: / / gdc-portal.nci.nih.gov / ) were obtained and analyzed for the presence of frameshift mutations (FSM) in MNRs located within protein-coding segments of the exome of protein-coding genes that were equal to or longer than 6 nucleotides. Only tumors with an MSI phenotype as defined in the TCGA sample annotation data were considered in the analysis. The set included a total of 320 tumor and matched normal control samples, corresponding to 69 MSI-high (MSI-H) colorectal cancer (CRC), 85 MSI gastric cancer, and 166 MSI endometrial cancer (EC), respectively. In the second filtering step, only FSMs derived from 1-nucleotide deletions were accepted, as this type of FSM is most common in CRC and ...

Embodiment 2

[0321] Example 2: Selection of a list of frameshift peptides with acceptable properties

[0322] Then use ANNOVAR to map each FSM of the CFSM selected in Example 1 to the corresponding mRNA sequence (or sequences) from the NCBI REFSEQ database (Wang K, et al. (2010) NAR, 38: e164), and Wild-type (wt) and resulting mutant mRNAs are translated into protein. Comparison of wt and mutated protein sequences allowed determination of the amino acid (aa) sequence of the corresponding frameshift peptide (FSP). When the FSM produced multiple FSPs with different lengths and / or aa sequences due to the presence of multiple mRNA isoforms, all resulting FSPs were retained. The resulting list was filtered to exclude all FSPs shorter than 4 aa, which cannot generate potential CD8T neo-epitopes.

[0323] In addition, the amino acid sequence of the FSP included in the CVP is modified by adding or deleting amino acids if the following conditions are met (or FSPs that do not satisfy certain condi...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

This invention relates to a method of selecting a collection of frame- shift peptides (CFSPs) to produce a universal cancer vaccine peptide collection (CVP) for prophylaxis and treatment of patients with hereditary and sporadic micro- satellite instability (MSI) tumors. This invention relates as well to a method of producing a CVP by selecting a subset of frame-shift peptides (FSPs) from the CFSPand optionally modifying the FSP's amino acid (aa) sequence to generate modified FSPs (mFSPs). The invention further relates to nucleic acid collections encoding a CVP of FSPs and / or mFSPs in one or more vaccine vectors that can be used also simultaneously. These CVPs, nucleic acids and vectors are used for the prophylaxis or treatment of MSI cancers.

Description

[0001] The present invention relates to a method of selecting a collection of frameshift peptides (CFSP) to prepare a universal cancer vaccine peptide collection (CVP) for the prevention and treatment of hereditary and sporadic microsatellite instability (MSI) tumors of patients. The present invention also relates to a method of preparing CVP by selecting a subset of frameshift peptides (FSP) from CFSP and optionally modifying the amino acid (aa) sequence of the FSP to generate a modified FSP (mFSP). The invention also relates to a collection of nucleic acids encoding CVP with FSP and / or mFSP in one or more than one vaccine vectors which can also be used simultaneously. These CVPs, nucleic acids and vectors can be used to prevent or treat MSI cancer. [0002] Background of the invention [0003] The field of cancer vaccines has long focused on targeting tumor-associated and, more recently, tumor-specific antigens. The latter can be caused in cancer cells by somatic mutations ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): G16B20/00C07K14/47
CPCC07K14/4748G16B20/00A61K39/0011A61K2039/5152G16B30/10A61K38/08A61K38/10A61K38/04A61K38/16C12N15/00C07K7/00
Inventor 阿尔弗雷多·尼科西亚埃莉萨·斯卡尔塞利圭多·莱昂尼阿明·拉姆
Owner NOUSCOM AG
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com