184 results about "Neo antigens" patented technology

Disclosed herein are chimpanzee adenoviral vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

The invention provides a new antigen immunogenicity prediction method and system based on multi-feature fusion, and belongs to the technical field of machine learning, and the method comprises the steps: inputting a candidate peptide fragment sequence into an antigen intracellular processing prediction model to obtain a score representing the intracellular processing capability; inputting the candidate peptide fragment sequence into a pre-trained Transform model to obtain a sequence vector representation of the candidate peptide fragment; training an immunogenicity prediction model by taking the immunogenicity related characteristics, the sequence vector representation of the candidate peptide fragment and the score representing the intracellular processing capacity as a training sample; and screening the target candidate peptide fragment sequence by using the immunogenicity prediction model to obtain the tumor neoantigen. According to the method, the scoring model special for evaluating the intracellular processing and presentation capacity of the antigen peptide is constructed, the scoring model is output as a key feature, efficient fusion and learning are carried out on the key feature, multiple immunogenicity-related biological features and sequence vector representation of candidate peptide fragments, and the accuracy and reliability of tumor neoantigen immunogenicity prediction can be remarkably improved.

The invention relates to the technical field of bioinformatics, and discloses a method, a system, equipment and a medium for searching for base mutation aiming at third-generation full-length transcript sequencing data, the base mutation is accurately positioned to a specific transcript by directly processing the third-generation full-length transcript sequencing data, and the method and the system for searching for the base mutation aiming at the third-generation full-length transcript sequencing data are provided. The co-occurrence relation of a plurality of mutations on the same transcript is accurately analyzed, and the defects of calculation redundancy, function misjudgment and the like caused by the fact that a mutation transcript source cannot be determined due to fragmentation splicing and the co-occurrence is simulated by depending on permutation and combination in a second-generation short-read-long sequencing technology are effectively overcome; the recall rate of transcripts which are not mapped due to a high-variation region is improved through mapping correction assisted by structural variation, and false positive is effectively inhibited through a multi-dimensional filtering condition, so that the sensitivity and reliability of mutation detection are remarkably improved; particularly, mutation events with function remodeling due to reading frame change can be accurately recognized in scenes such as neoantigen prediction where mutation function consequences need to be accurately evaluated, and the method has important value in application in the fields of precision medical treatment and the like.

The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether a modification in a peptide or polypeptide, such as a tumor-associated neoantigen, is immunogenic. The methods of the present invention are particularly suitable for providing a vaccine specific to a patient's tumor and, therefore, are suitable for use in the context of personalized cancer vaccines.

A system and corresponding method are provided for identifying a subpopulation of cancer patients who are immunotherapy respondents using a more effective method of assessing neoantigen presentation. Such a method will also enable the creation of more effective therapies, such as vaccines, based on presented neoantigens.

Cancer immunology provides promising new avenues for cancer treatment but validation of potential neoantigens to target is costly and expensive. Analysis of MHC binding affinity, antigen processing, similarity to known antigens, predicted expression levels (as mRNA or proteins), self-similarity, and mutant allele frequency, provides screening method to identify and prioritize candidate neoantigens using sequencing data. Methods of the invention thereby save time and money by identifying the priority candidate neoantigens for further experimental validation.

The present disclosure provides methods for producing engineered immune cells, engineered immune cell populations, and methods of using the engineered immune cells for treating subjects with cancer and other conditions. The engineered immune cells provided herein can comprise antigen-specific T cells (e.g., neoantigen-specific T cells), TCR-T cells, or CAR-T cells. The engineered immune cells prepared by the methods provided herein can exhibit beneficial phenotypes, such as increased persistence, increased effector function, increased activation function, and / or lower dysfunction.

The invention discloses a tumor neoantigen accurate analysis method and system based on multi-dimensional evidence chain scoring, and relates to the cross technical field of bioinformatics, computational biology and tumor immunology, and the system comprises a multi-dimensional evidence chain scoring module which is used for evaluating the feasibility score of candidate neoantigens; the antigen extraction and verification module is used for identifying and verifying a tumor specific antigen according to the feasible degree score; the anchoring site identification and prediction module is used for scoring the amino acid of each site by using an amino acid frequency weighted BLOSUM62 coded value, obtaining a specific anchoring site and an anchoring site amino acid residue restriction set, and judging whether a certain peptide fragment is a non-binding peptide or not according to the specific anchoring site and the anchoring site amino acid residue restriction set so as to obtain a judgment result; the intelligent MHC retrieval module is used for enabling a user to input a character string at the front end according to the judgment result to conduct intelligent retrieval so as to obtain a retrieval result, and high-precision recognition and evaluation of the tumor neoantigen are achieved.

The present invention relates to methods for predicting whether peptides or polypeptides comprising disease specific amino acid modifications, in particular tumor-associated neo-antigens, comprise epitopes, in particular tumor-associated neo-epitopes, which are useful for immunotherapy such as for vaccination. The methods of the invention may be used, in particular, for the provision of vaccines which are specific for a patient's tumor and, thus, in the context of personalized cancer vaccines.

Indivi dualized neoantigen vaccines, as well as methods for their use in subjects to treat urothelial orbladder cancer are provided. In some embodiments, individualized neoantigen vaccines are used with an immune checkpoint inhibitor and optionally enfortumab vedotin to treat a urothelial or bladder cancer after surgical resection. Prior to surgical resection, in some embodiments, the subject is administered a neoadjuvant therapy comprising an immune checkpoint inhibitor, individualized neoantigen vaccines, and, optionally, enfortumab vedotin.

The present invention provides a TCR targeting a KIT D816Y mutation-derived neoantigen, a nucleic acid molecule comprising a nucleotide sequence encoding the TCR or a complementary sequence thereof, a vector containing the nucleic acid molecule, and a cell transduced with the nucleic acid molecule or the vector, as well as a pharmaceutical composition comprising the TCR, nucleic acid molecule, vector or cell as an active ingredient, and use of the TCR, nucleic acid molecule, vector, cell and pharmaceutical composition in detecting, preventing and / or treating cancers associated with KIT D816Y gene mutation-derived neoantigens.

The present application provides a TCR targeting a FLT3D835H mutation-derived neoantigen, a nucleic acid molecule comprising a nucleotide sequence encoding the TCR or a complementary sequence thereof, a vector containing the nucleic acid molecule, a cell transduced with the nucleic acid molecule or the vector, a pharmaceutical composition comprising the TCR, the nucleic acid molecule, the vector or the cell as an active ingredient, and use of the TCR, the nucleic acid molecule, the vector, the cell or the pharmaceutical composition in detection, prevention and / or treatment of a cancer related to a FLT3D835H gene mutation-derived neoantigen.

The present disclosure relates to neoplasia vaccine or immunogenic composition administered in combination with other agents, such as checkpoint blockade inhibitors for the treatment or prevention of neoplasia in a subject

The present invention relates to a combined treatment composition for tumor treatment and a combined treatment method. The combined treatment composition or a medicine kit comprises a therapeutically effective amount of a platinum chemotherapeutic drug, and a therapeutically effective amount of CpG oligonucleotide and a therapeutically effective amount of R848. The present invention further provides a combined treatment method for treating a tumor by means of the combined treatment composition or the medicine kit. Firstly, a low-dose chemotherapeutic drug is used to kill a tumor so as to release a tumor neoantigen, such that a body immune system autonomously identifies and screens the neoantigen, and then CpG oligonucleotide and an R848 activator of immune response are used to induce and promote the body to generate immune response specific to the tumor neoantigen, such that the anti-tumor function of T cells is improved and enhanced, thereby achieving the effect of inhibiting tumor growth.

The present invention provides phagocytic particles for treating or preventing cancer in a subject, wherein the phagocytic particle comprises a core and a neoantigen construct tightly associated with the core, and wherein the neoantigen construct comprises a neoepitope peptide having an amino acid sequence corresponding to the amino acid sequence of a portion of a protein or peptide known or suspected to be expressed by a cancer cell in the subject, wherein the portion of the protein or peptide has at least one somatically mutated amino acid. The present invention also relates to an injectable pharmaceutical composition for treating or preventing cancer.

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and / or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and / or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

The present disclosure provides compositions and methods for targeting a neoantigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as T cell receptors, that bind to a neoantigen:HLA complex. The binding proteins further comprise a construct comprising a fusion protein of a CD95 ectodomain and a CD137 intracellular signaling domain (Fas-41BB), and a CDS co-receptor α or β chain. The disclosed binding proteins are highly sensitive to antigen, and are capable of inducing activation of host T cells at low concentrations of peptide antigen. In certain embodiments, binding proteins of the present disclosure are non-alloreactive against, are substantially non-alloreactive against, and / or have a low risk of alloreactivity against (i) amino acid sequences from the human proteome and / or (ii) against human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers.

A system and corresponding method are provided for identifying a subpopulation of cancer patients who are immunotherapy respondents. An effective method of assessing neoantigen presentation is provided. A vaccine composition is also provided. The vaccine composition is prepared by feeding data for a subject with a type of cancer into a predictive model and scoring neoantigens that occur in data for the subject for one or more parameters. One or more vaccine compositions to be administered to the subject are prepared for one or more somatic mutations for one or more neoantigens that satisfy an immune stimulation threshold.

This invention belongs to the field of biomedical technology, specifically disclosing the application of a CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid in the preparation of a drug for treating tumors. Through analysis of the COSMIC database, epitope prediction, and in vitro and in vivo immunomodulatory activity experiments, this invention identified an HLA-A2-restricted CTL epitope peptide derived from the neoantigen ESR1. This mutant epitope peptide originates from a high-frequency mutation of ESR1 and can effectively stimulate and induce the production of neotope-specific cytotoxic T lymphocytes, specifically distinguishing between wild-type and mutant sequences, and killing tumor cells expressing the mutant epitope, exhibiting good anti-tumor effects. The resulting drug for treating tumors may contain the CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid, or may contain a T-cell receptor, chimeric antigen receptor, or its encoded nucleic acid that specifically recognizes the mutant epitope peptide, demonstrating good therapeutic potential and clinical application prospects.

A method of ranking epitopes derived from neoantigens as targets for personalized immunotherapy includes collecting candidate epitopes based on patient data of a cancer patient. A set of scores are calculated for each of the candidate epitopes, each of the scores in a respective one of the sets for a respective one of the candidate epitopes representing an independent measure of a likelihood of the respective one of candidate epitopes to elicit an immune response in the cancer patient. The scores in each of the sets of scores are combined into a single score for each of the candidate epitopes. The single scores for the candidate epitopes in each case reflect an overall likelihood of eliciting the immune response in the patient. The candidate epitopes are ranked using the single scores for the immunotherapy.

The present disclosure relates to methods of culturing immune cells, e.g., T cells, NK cells, and / or TILs, for an immune cell therapy, wherein the immune cells are contacted with a CD28 agonist, and wherein the immune cells are not contacted with a CD3 agonist. In some aspects, the methods disclosed herein promote the enrichment of immune cells having a less-differentiated phenotype, i.e., expressing markers characteristic of stem cell-like memory T (Tscm) cells. Cells cultured using the methods disclosed herein can be used for various cell therapies, including but not limited to chimeric antigen receptor (CAR) T cell therapy and TCR T cell therapy, including neoantigen directed-T cell therapies.

Provided are methods for treating cancer by administrating to an individual who has the cancer an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and an immune checkpoint inhibitor. Also provided are methods for promoting translation of proteins within cells such that proteins include one or more misincorporated amino acids to thereby develop new proteins that contain neoantigens. Vaccines that include the neoantigens are included. Methods for producing and detecting misincorporation of a tyrosine in proteins expressed by cells are also provided.

The invention discloses a tumor tissue splicing recognition and neoantigen peptide screening method based on an ONT sequencing platform, and belongs to the technical field of tumor immunology. Comprising the following steps: extracting RNA from a tumor tissue, separating mRNA, constructing a sequencing library, and sequencing through an ONT sequencing platform to obtain original data; performing basic group identification on the original data to obtain fastq format data; comparing the data to a reference genome reconstruction transcript, identifying a variable splicing event based on a comparison result, and performing difference analysis; screening out variable splicing events with significant differences, and extracting novol transcript coding sequences related to the events; extracting a 9mer peptide fragment crossing a splicing site in a splicing boundary region of the transcript; performing MHC binding affinity scoring on the peptide fragments, and screening out candidate new antigen peptide fragments; and carrying out mass spectrum verification on the candidate new antigen peptide fragment, and screening the actually expressed peptide fragment. The method can be widely applied to tumor immunomarker screening, new antigen vaccine design and individualized treatment strategy development.

Disclosed herein are presentation models useful for identifying and selecting class II neoantigens that are likely presented by a set of MHC alleles expressed by a patient. Methods disclosed herein are useful for generating personalized cancer vaccines. Specifically, the disclosed presentation models leverage protein sequence embeddings across MHC alleles of the patient genotype. A learned genotype network (“LGN”) of the presentation model aggregates embeddings from all class II HLA alleles prior to prediction. The learned genotype network generates a prediction vector that can be used to predict likelihood of presentation of epitope sequences.

The present invention provides a method for expanding anti-tumor T cells comprising the steps of: a) providing a phagocyzable particle having one or more tumor neoantigen constructs in intimate association therewith wherein the tumor neoantigen constructs comprise an amino acid sequence comprising at least one mutant amino acid known or suspected of being associated with cancer in a subject, or a mutated or non-mutated amino acid sequence known or suspected of expression in cancer cells of the subject; b) providing a living antigen presenting cell; c) contacting the particles with the antigen presenting cells in vitro under conditions that allow the antigen presenting cells to phagocytize the particles; d) providing a T cell sample comprising live T cells from the subject; e) contacting the T cell sample with the antigen presenting cells in in vitro contact with the particles under conditions allowing specific activation of the anti-tumor T cells in response to the antigen presented by the antigen presenting cells. The invention also provides tumor neoantigen constructs as defined in the specification.

A method of treating a subject having been diagnosed as having cancer with an immunotherapy is described. The method comprises targeting one or more clonal neoantigens selected using a method comprising determining whether a tumour-specific mutation is likely to be clonal in a subject. The method comprises providing sequence data from one or more samples from the subject comprising tumour genetic material, the sequence data comprising for each of the one or more samples, and determining the likelihood that the tumour-specific mutation is clonal as a posterior probability depending on: a prior probability of the mutation being clonal, and the probabilities of observing the sequence data if the tumour-specific mutation is (i) clonal and (ii) non-clonal, in view of a tumour fraction for each of the one or more samples and one or more candidate joint genotypes.

Compositions, kits, and methods that implement neoantigens specific to cancer cells having recurrent mutations in SRSF2 or ZRSR2, wherein the mutations are shared across patients with those mutational genotypes, as well as cognate T cell receptors (TCRs) that specifically recognize those neoantigens.