383 results about "Neo antigens" patented technology

A compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof wherein X-Y is -NHSO2- or -SO2NH-; R1 is H, CN or alkyl; R2 is selected from COOH and a tetrazolyl group; R3 is selected from H, Cl and alkyl; R4 is selected from H and halo; R5 is selected from H, alkyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R6 is H; R7 is selected from H, CN, haloalkyl, halo, SO2-alkyl, optionally substituted heteroaryl, SO2NR14R15, CONR10R11 and alkyl; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H or halo; and R10, R11, R12, R14, and R15 are H or alkyl; R13 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m is 0-3. The compounds of formula (I) modulate ERAP1 (endoplasmic reticulum aminopeptidase 1) and are for use in treating proliferative, immune or inflammatory disorders, particularly cancer or leukemia. The compounds of formula (I) stimulate a neo-antigen directed immune response in the subject. A method for producing an antigen-presenting cell which presents a neo-antigen using compounds of formula (I) is disclosed. An immunogenic composition comprising an antigen-presenting cell is also disclosed. Exemplified compounds include 4-cyclopropyl-3-(N-(2-(morpholin-3-yl)-5-(trifluoromethyl)phenyl)sulfamoyl)benzoic acid.

The invention relates to the technical field of biological information, in particular to an immunoreaction evaluation method based on tumor neoantigen activity sorting. The method comprises the following steps: obtaining genome data of tumor and normal tissues through whole exon sequencing, extracting multi-dimensional features of candidate somatic mutation, and screening by combining a Gaussian mixture model and a Transform model to obtain a high-confidence mutation genome set; predicting the HLA genotype of a patient based on sequencing data, translating and mutating into a peptide fragment, predicting the binding affinity of the peptide fragment and an MHC molecule by using an XGBoost model, and calculating a new antigen activity score sequence in combination with various parameters; and finally, synthesizing a new antigen peptide fragment according to a sorting result, carrying out in-vitro co-culture to detect an IFN-gamma secretion result, and dynamically optimizing a characteristic combination coefficient through a PPO algorithm to realize intelligent iterative updating, so that the accuracy of new antigen screening and the immunoreaction prediction capability are remarkably improved.

The invention belongs to the field of biological medicine, and particularly relates to a mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition and application of the mouse MC38 colorectal cancer neoantigen polypeptide and immunologic adjuvant composition in tumor treatment, and amino acid sequences of the neoantigen polypeptide are shown as SEQ ID No.2, 13, 16 and 17. Four tumor neoantigen polypeptides really having immunogenicity are obtained through screening, the obtained tumor neoantigens are compatible with PolyI: C to prepare the vaccine preparation, and after mice are treated by the MC38 tumor vaccine preparation, the growth of tumors can be effectively inhibited; and the survival time of the mouse is prolonged, and the new antigen vaccine preparation generates very effective T cell reaction in the tumor-bearing mouse body.

The present invention relates to bispecific antigen binding molecules specific for both the receptor tyrosine kinase-like orphan receptor 1 (ROR1) and the epidermal growth factor receptor (EGFR), as well as related fusion proteins and conjugates. In another aspect, the invention relates to conjugated immunoglobulin-like shark variable neoantigen receptors (VNARs).

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.

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.

The invention relates to the technical field of tumor neoantigen detection, and particularly discloses a neoantigen prediction method and system for a malignant solid tumor, and the method comprises the following steps: obtaining a tumor sample and a peripheral blood sample, and carrying out DNA and RNA sequencing; analyzing and processing to obtain DNA (Deoxyribonucleic Acid) sequencing data and RNA (Ribonucleic Acid) sequencing data; analyzing to obtain an HLA typing result and a sequence of the mutant protein; calculating to obtain related characteristic values of the new antigens; calculating a new antigen score; and intercepting the first N pieces with the highest scores to obtain a neoantigen prediction result of the malignant solid tumor. Starting from the action mechanism of the new antigens, according to key steps of the prediction process, a plurality of characteristic values are selected, a hard filtering index is not adopted, a product mode is adopted, and the score of the new antigens is calculated according to the score of the relevant characteristic values of the new antigens.

Drug delivery nanoparticle compositions and methods for the treatment of a cancer are provided that can be used individually or in combination. These compositions and methods include: (1) exogenous vaccination using neoantigens or tumor-associated antigens to potentiate an anti-tumor immune response; (2) nanoparticle-based drug delivery targeting the liver, aimed at reprogramming the hepatic immune environment to reduce or eliminate tumor antigen tolerance, thereby enhancing the immune system's ability to combat metastatic cancer; and (3) expansion of the liver metastasis treatment platform to target tumor-associated lymphoid structures, supporting the immune response at the primary tumor site. Any of these methods may be optionally combined with chemo-immunotherapy for enhanced efficacy.

The invention belongs to the technical field of biomedicine, and particularly relates to tumor neoantigen polypeptide based on EGFR gene mutation and application of the tumor neoantigen polypeptide. According to the effective method for predicting and screening the tumor neoantigen by using the tumor neoantigen prediction platform, the specific mutation of tumor tissues is obtained, and the neoantigen polypeptide with high immunogenicity, high affinity and high activation effect is more accurately predicted; the screened new antigen polypeptide makes up the blank of individualized antigen peptide in treatment of lung cancer NSCLC patients with EGFR-L858R somatic mutation, can be synthesized in a large scale, is used for subsequent standardized and individualized immunotherapy of EGFR-L858R mutation tumor patients, and has a good clinical application prospect.

Immunogenic targets associated with one or more types of cancer, wherein the immunogenic target includes a shared splicing amino acid-based neoantigen present in any of SEQ ID NOs: 1-2545, or a nucleotide coding therefor, are described, as well as uses thereof, and methods of identifying such immunogenic targets. Particular embodiments relate to immunotherapies for treating a type of cancer, and methods of treating a type of cancer by administering such immunotherapies, wherein the immunotherapy includes an immunogenic target including a shared splicing amino acid-based neoantigen present in any of SEQ ID NOs: 1-2545, or a nucleotide coding therefor.

The present invention relates to the ranking / selection of tumor-specific neoantigens of a subject having cancer. The present invention also provides methods using the ranked / selected tumor-specific neoantigens in. for example. the treatment or prevention of cancer. Ranked and selected neoantigens may be used as biomarkers in the diagnosis, monitoring and / or prognosis of tumor diseases.

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 provides a method for screening a potential neoantigen of a tumor from a transposon element. The method comprises the following steps: collecting tumor tissue transcriptome sequencing data and normal tissue transcriptome sequencing data; identifying a TE transcript new type TEtrans based on a TE splicing event; performing feature analysis on the TEtrans; the TEtrans with the potential coding capability is screened out; and identifying the new antigen epitope peptide from the TEtrans: hydrolyzing all open reading frames of the to-be-selected TEtrans into 9 peptides which are mutually overlapped, removing annotated peptide fragments contained in Uniprot, defining the new antigen epitope peptide from the TEtrans according to allele typing of a tumor sample, further comparing the new antigen from the TEtrans with three common new antigens from genomic variation sources, and identifying the new antigen from the TEtrans. And screening to obtain the tumor potential new antigen. According to the invention, a brand new intergene region TE source transcript is successfully identified, and the transcript can be uniquely positioned and accurately quantified, so that a tumor specific transcript is screened as a potential tumor new antigen, and the method has huge potential in the aspect of developing tumor new antigen vaccines, especially tumors with low mutation load.

The invention relates to the field of intelligent medical treatment, in particular to a new antigen screening method, equipment and a program product. Comprising the following steps: S1, acquiring tumor slice data and serum data of a patient; s2, performing data processing on the tumor slice data and the serum data to obtain an HLA / MHC pseudo sequence, antigen peptide data and an antigen gene expression level; the data processing comprises data sequencing, HLA / MHC typing, somatic mutation calculation, fusion gene calculation and gene expression profile calculation; s3, screening new antigens based on the HLA / MHC pseudo sequence, the antigen peptide data and the antigen gene expression level data to obtain the new antigens, the application can perform new antigen screening, and has good clinical value.

The invention discloses an HLA and antigen peptide combination prediction method based on interactive attention, and belongs to the technical field of computational biology. The method comprises the following steps: 1, collecting HLA allele and unique peptide fragment data, and constructing an HLA and antigen peptide binding data set; 2, constructing an HLA and antigen peptide binding prediction model, and training the prediction model by using the HLA and antigen peptide binding data set to obtain a trained prediction model; and step 3, inputting the HLA sequence and the antigen peptide sequence into the prediction model to obtain a prediction result of combination of the HLA and the antigen peptide. According to the method, prediction tasks based on a sequence and a structure are integrated into a unified model, and the potential of the pHLA about the sequence and the structure is analyzed and predicted. Compared with an existing method, the two-dimensional evaluation provides a more comprehensive antigen immunogenicity view angle, and a new insight is provided for the quality of a new antigen for triggering an immunoreaction.

The invention discloses a method for performing sarcoma high-frequency neoantigen function verification based on tumor organoids, and the method for performing sarcoma high-frequency neoantigen function verification based on tumor organoids comprises the following steps: after separating PBMC, enriching CD8 + T cells, and stimulating the CD8 + T cells by using DC loaded with candidate neoantigen polypeptide to obtain neoantigen specific CTL; new antigen-specific CTL is tested through the kit, secretion of IFN-gamma is detected, and antigen-specific CTL with positive reaction is screened out; the method comprises the following steps: selecting a candidate new antigen capable of specifically stimulating CTL to generate an IFN-gamma positive reaction according to an experiment result of secreting IFN-gamma by the CTL, establishing a tumor organoid-CTL cell co-culture system, setting PBMC primary T cells of a patient which are not stimulated by DC loaded with the candidate new antigen as a control group, and measuring organoid light microscope radiography and tumor cell death conditions. The function of the sarcoma high-frequency neoantigen is evaluated based on tumor organs.

The present disclosure provides compositions and methods for targeting neoantigens, for example, to treat or prevent cancer. The disclosed embodiments include binding proteins, such as T cell receptors, that bind to the neoantigen: HLA complex. The binding protein further comprises a construct comprising a fusion protein of the CD95 extracellular domain and the CD137 intracellular signaling domain (Fas-41BB), and a CDS coreceptor alpha or beta chain. The disclosed binding proteins are highly sensitive to antigens and are capable of inducing activation of host T cells at low concentrations of peptide antigens. In certain embodiments, binding proteins of the present disclosure (i) have no alloreactivity, substantially no alloreactivity, and / or low risk of alloreactivity, to amino acid sequences from human proteomes and / or (ii) to human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into host cells, such as T cells, and the cells can be used in immunotherapy for the treatment of various cancers.

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 invention discloses a tumor nano vaccine (BAPs) of bionic autophagosome as well as a preparation method and application thereof, and the vaccine effectively stimulates anti-tumor immunity by precisely fusing a neoantigen derived from the autophagosome and an immunologic adjuvant targeted lymph node. The BAPs with the redox response characteristic promote the vaccine to be opened in antigen presenting cells, so that an adjuvant and an antigen are exposed, and a strong immune response is stimulated. The BAPs can excite wide T cell reactions, and finally, more than 70% of established tumors are effectively eliminated. BAPs vaccination initiates a lasting T cell reaction and provides powerful protection, all mice are protected in tumor recurrence challenge, and the tumor incidence rate is significantly reduced by nearly 90%. In addition, the BAPs and a checkpoint inhibition therapy have a synergistic effect, and growth of breast cancer with poor immunogenicity is inhibited. The BAPs nano vaccine provides an efficient strategy with clinical transformation potential to enhance the strong immune response of personalized cancer immunotherapy.

The present disclosure provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

Systems and methods for determining the likely responsiveness of a human cancer subject to a checkpoint blockade immunotherapy regimen are provided. Sequencing reads are obtained from samples from the subject representative of the cancer. A human leukocyte antigen type and a plurality of clones is determined from the sequencing reads. For each clone, an initial frequency Xα in the one or more samples is determined and a corresponding clone fitness score of the clone is computed, thereby computing clone fitness scores. Each such fitness score is computed by identifying neoantigens in the respective clone, computing a recognition potential for each neoantigen, and determining the corresponding clone fitness score of the respective clone as an aggregate of these recognition potentials. A total fitness, quantifying the likely responsiveness of the subject to the regimen, is computed by summing the clone fitness scores across the plurality of clones.

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.

The present disclosure provides methods of determining whether a tumour-specific mutation is likely to be clonal in a subject. The method comprise determining, by a processor, a metric indicative of the probability that the mutation is clonal by combining evidence from sequence data obtained from the subject and an indication of whether the mutation is associated with one or more predetermined mutational signatures. The methods may be used to identify clonal mutations and clonal neoantigens in a subject, and to design immunotherapies that target clonal neoantigens. Related methods, systems and products are also described.

The invention relates to the technical field of tumor vaccines, and provides a novel mRNA (messenger Ribonucleic Acid) tumor vaccine for treating mouse liver cancer, which is prepared by the following steps: S1, specific neoantigen prediction: carrying out bioinformatics analysis on a next-generation sequencing database of tumor patients in the hospital, and selecting tumor specific neoantigens through the following steps; s11, low-quality readings are removed through a filtering step; s12, detecting single nucleotide variation by using a Mutect method and a VarScan method; s13, annotating missense mutation by using ANNOVAR software; in-vivo and in-vitro experiments prove that the vaccine has a remarkable anti-tumor effect, is designed and synthesized aiming at a newly screened new antigen mutation sequence and has high specificity and pertinence, and experimental results show that the vaccine can remarkably improve immune response of specific CTLs cells, induce T cell response of new antigen specificity, and has a good anti-tumor effect in a tumor-bearing mouse model. The vaccine has a remarkable inhibiting effect on tumor growth, and the problems in the prior art are solved through the technical scheme.

The invention relates to a tumor neoantigen DC vaccine based on a cytoskeleton as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The neoantigen DC vaccine comprises a cell scaffold which is formed by a polymer material and has a porous spongy structure, bone marrow-derived dendritic cells BMCD and tumor neoantigen which are dispersed in the cell scaffold, and an active substance which is cross-linked with the cell scaffold and is used for promoting proliferation and differentiation of T cells or B, the active substance comprises CCL21, and the tumor neoantigen is derived from liver cancer cells. According to the novel antigen DC vaccine based on the cytoskeleton, recruitment of T cells is realized in vivo, interaction of DC-T is promoted, and novel antigen specific T cells are efficiently induced and activated; moreover, the cell scaffold can simulate an immune microenvironment of lymph nodes through in-vivo implantation, so that an anti-tumor effect based on neoantigen DC vaccine excitation is realized.

The invention relates to a tumor neoantigen prediction method and a tumor neoantigen prediction system. The method comprises the following steps: acquiring a plurality of amino acid sequences in a gene of a person to be tested as a plurality of test peptides to be compared with a plurality of human protein sequences in a protein sequence database so as to find out a plurality of similar peptides matched with the human protein sequences; filtering similar peptides from the test peptides, and respectively inputting the filtered test peptides into a plurality of trained human leukocyte antigen models to obtain a plurality of sequencing results of the test peptides; calculating the weighted sum of the sequencing of each test peptide in the sequencing result as the score of the test peptide; and selecting at least one of the test peptides as a neoantigen suitable for the subject according to the fraction.

The present disclosure relates to a method for designing a personalized cancer vaccine, using a B cell-reactive neoantigen, the method comprising the steps of: receiving a peptide sequence extracted from cancer tissue and allelic sequence data of B cell receptors; calculating the preferential binding strength between amino acids in the peptide sequence and allelic sequences of B cell receptors; and calculating B cell epitope prediction scores by inputting the preferential binding strength between amino acids to a trained neural network model.

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.

The invention discloses a preparation method of infiltrating lymphocytes with high proportion of neoantigen reactive T cells. The proportion of the reactive T cells with tumor neoantigen specificity can be increased without using a gene editing technology. In the TIL cell culture process, DC presents tumor neoantigen and TIL is sorted and cultured, the proportion of T cells with neoantigen reactivity in TIL is increased, the anti-tumor activity of the TIL cell preparation is enhanced, then the prepared infiltrated lymphocytes are rapidly and massively amplified, and the TIL cell preparation has the advantages that the tumor neoantigen reactivity is improved. And batch preparation of the neoantigen reactive TIL cell preparation with high reactivity to tumors is facilitated.