25 results about "Neo epitope" patented technology

The invention belongs to the technical field of immunodetection, and discloses a kit for detecting the ratio of proBDNF to maure BDNF based on structural dynamics guidance and a preparation method of the kit, the kit comprises a solid phase carrier and a detection reagent, the three antibodies are determined on the basis of full-length conformational kinetics analysis of brain-derived neurotrophic factors; the first capture antibody targets an innate disorder region (SEQ ID NO: 1) of a proBDNF propeptide region; the second capture antibody targets an innate disorder region (SEQ ID NO: 2) of a proBDNF propeptide region; the second capture antibody is a neo-epitope specific antibody, is specifically combined with an N terminal (SEQ ID NO: 2) exposed by maure BDNF enzyme digestion, and is combined with a free alpha-amino group strictly dependent on the first histidine; and the universal detection antibody is combined to a Loop 4 region (SEQ ID NO: 3) of the Mature structural domain. The problems of steric hindrance and cross reaction in traditional immunodetection are solved through a structural biology strategy, and accurate distinguishing and ratio quantification of proBDNF and maure BDNF are achieved.

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.

Systems and methods are presented that allow for determination and prediction of payload toxicity in therapeutic viruses. Disclosed herein are methods of determining payload toxicity of an expressed polypeptide in a cell, comprising: generating or procuring a plurality of expression vectors, each containing a different recombinant nucleic acid sequence that encodes a corresponding recombinant polypeptide; expressing the recombinant nucleic acid sequence in a plurality of host cells while culturing the host cells; sequencing the plurality of expression vectors after culturing the host cells; and correlating at least portions of the recombinant nucleic acid sequence with a toxicity measure.

The application provides preparation and application of a diagnostic monoclonal antibody for a new epitope of human neutrophil lipocalin (HNL). Two new HNL protein conformation epitopes and one new HNL linear epitope are designed and provided, and an anti-HNL antibody with higher binding affinity and better binding specificity is screened to combine the new epitopes. The anti-HNL antibody of the application can be used for preparation of an HNL detection reagent and kit, and has higher sensitivity and specificity when used for detecting HNL protein in a sample, and can be applied to distinguishing bacterial infection and viral infection.

Effectiveness of a neoepitope-based immunotherapeutic composition against a tumor can be increased by predicting the surface presentation of the neoepitope bound to the HLA molecule of the tumor cell. Surface presentation levels of neoepitopes can be predicted by identifying any changes in omics data of the tumor cell that may affect the expression or surface trafficking of the HLA molecule and that may affect binding affinities of neoepitopes to the HLA molecule.

The disclosure provides a method for detection and quantification of amyloidogenic lambda free light chain (lFLC). The disclosure further provides reagents for performing the method, including monoclonal antibodies or antigen binding fragments thereof that bind to a neo-epitope on amyloidogenic λFLC exposed to limited proteolysis. The clinical utilities of the methods described herein include early detection in individuals suspected of plasma cell disorders (MGUS, SMM, MM, IgM-AL, and AL), differentiation from other amyloidosis such as ATTR, use in companion diagnostics, demonstration of target engagement, assessment of therapeutic response, detection of MRD, and detection of relapse.

Compositions of peptides modified to improve HLA binding or T cell recognition while conserving reactivity to the target neoepitope, enhance activation of neoantigen-specific T cells. Methods of use include treating cancer by administering one or more of these peptides generated by computer modeling.

Provided is a modified peptide composition which is modified to enhance HLA binding or T cell recognition and improve activation of neoantigen-specific T cells while preserving reactivity to a target neoepitope. Methods of use include the treatment of cancer by administering one or more of these peptides generated by computer modeling.

A method for combining restrictive proteolysis and immunoassays to specifically detect and quantify amyloid-genic XFLC in a biological fluid. This method is accomplished by the use of mAbs that enable the detection and quantification of neoepitopes on dLCCD biomarkers produced after restricted proteolysis of ZFLC, which is very advantageous for kinetically unstable or amyloid-genic LFLC. The methods do not depend on FLC primary sequences in variable and constant domains, and can be used to detect and quantify up to 99% of human XFLC. The clinical utility of the assay includes early detection in individuals suspected of having plasma cell disorders (MGUS, SMM, MM, IgM-AL and AL), differentiation from other amyloidosis such as ATTR, use in companion diagnosis, proving of target conjugation, assessment of treatment response, detection of MRD, detection of recurrence. Assays, such as MSD, lateral flow, mass spectrometry, are also implemented that quantify the resulting dLCCD biomarkers and / or can further increase assay sensitivity.

An assay measuring protease mediated degradation of type IV collagen and its biomarker potential for identifying cancer patients with a T-cell permissive tumor microenvironment is described.

This invention discloses an injury-related endogenous polypeptide and its applications. The invention employs a "single-model initial screening – multi-model cross-validation" strategy, using an acute lung injury (ALI) model as the screening set and partial hepatectomy (PHx) and cerebral ischemia-reperfusion injury (tMCAO) models as the validation set. Combined with liquid chromatography-tandem mass spectrometry (LC-MS / MS) technology, a group of serum endogenous polypeptides was screened. These polypeptides are novel epitope fragments generated by specific enzymatic digestion of precursor proteins such as fibrinogen α-chain and hemoglobin α / β subunits in the tissue injury microenvironment. Their expression levels are extremely low in healthy serum but exhibit explosive upregulation in injured states. Experiments have confirmed that this group of polypeptides shows significant responses in acute lung injury, liver injury, and cerebral ischemia-reperfusion injury models, and can serve as broad-spectrum biomarkers for multi-tissue injury, providing a novel detection target for the early diagnosis of multi-tissue injury in acute and critical clinical settings.

Described herein is an assay for measuring protease-mediated degradation of type IV collagen and its biomarker potential for identifying cancer patients with a T-cell permissive tumor microenvironment.

The present invention relates to the field of immunology and molecular virology, in particular the field of prevention and treatment of RSV. In particular, the present invention provides monoclonal antibodies capable of specifically binding to a new epitope between the pre-F protein and the V epitope or a new epitope between the II and the V epitope, and their use for the detection, prevention and / or treatment of RSV infection and / or diseases caused by said infection.

The application belongs to the technical field of immune detection, and discloses a kit for proBDNF and mature BDNF ratio detection based on structural dynamics orientation and a preparation method thereof. The kit comprises a solid carrier and a detection reagent, and is configured with three antibodies determined based on brain-derived neurotrophic factor full-length conformation dynamics analysis: a first capture antibody targeting an inherent disordered region (SEQ ID NO: 1) of a proBDNF propeptide region; a second capture antibody, which is a neoepitope specific antibody, specifically binds to an N terminal (SEQ ID NO: 2) exposed by mature BDNF enzyme cutting, and the binding is strictly dependent on a free alpha-amino group of the first histidine; and a universal detection antibody combined with a Loop 4 region (SEQ ID NO: 3) of a mature domain. The application solves the problems of spatial steric hindrance and cross reaction in traditional immune detection through a structural biology strategy, and realizes accurate differentiation and ratio quantification of proBDNF and mature BDNF.

The present disclosure relates to pharmaceutical compounds and compositions and methods for treating an allergy and Crohn's disease. Methods for treating an allergy can include (a) predicting potential epitopes based proteomes of microbiome and that of an allergen, (b) filtering the potential epitopes obtained in step a) to result in a list of epitopes; and (c) reengineering the list of epitopes obtained in step b) to result in the new epitope. Methods for treating Crohn's disease can include (a), identifying one or more binding regions of an HLA class II protein and / or hemagglutinin to I2 superantigen; (b) determining a first peptide sequence corresponding to the one or more binding regions, and (c) producing a peptide inhibitor having a second peptide sequence that is a mutation of the first peptide sequence, wherein the second peptide sequence has a stronger binding affinity to the I2 superantigen than the first peptide sequence.

The application belongs to the technical field of biological medicine, and specifically discloses application of a new antigen ESR1-derived CTL epitope peptide or coding nucleic acid thereof in preparation of a medicine for treating tumors. The application identifies and obtains an HLA-A2-restricted CTL epitope peptide derived from the new antigen ESR1 through analysis of a COSMIC database, epitope prediction and in-vivo and in-vitro immune activity experiments. The mutant epitope peptide is derived from a high-frequency mutation of ESR1, can effectively stimulate and induce production of a new epitope-specific cytotoxic T lymphocyte, specifically distinguishes between a wild type and a mutant sequence, kills tumor cells expressing the mutant epitope, and has a good anti-tumor effect. The medicine for treating tumors prepared therefrom can contain the new antigen ESR1-derived CTL epitope peptide or the coding nucleic acid thereof, or contain a T cell receptor, a chimeric antigen receptor or the coding nucleic acid thereof that specifically recognize the mutant epitope, and has good treatment potential and a clinical application prospect.

Systems and methods are presented that allow for determination and prediction of payload toxicity in therapeutic viruses. Contemplated methods of determining payload toxicity of an expressed polypeptide in a cell may comprise the steps of generating or procuring a plurality of expression vectors, each containing a different recombinant nucleic acid sequence that encodes a corresponding recombinant polypeptide; expressing the recombinant nucleic acid sequence in a plurality of host cells while culturing the host cells; sequencing the plurality of expression vectors after culturing the host cells; and correlating at least portions of the recombinant nucleic acid sequence with a toxicity measure.

The present invention relates to a peptide for treatment of the corona virus infection COVID-19 and a use thereof. In order to make the binding to the new epitope of SARS-CoV2 RBD stronger compared to the peptide (P6) simulating the conventionally known binding site between SARS-CoV RBD and ACE2, the peptide of the present invention includes a new portion added with a novel amino acid sequence fundamentally designed for interaction in the dimension of atoms consisting of the amino acids. Suggested in the present invention is a novel design of a peptide having higher binding affinity than conventionally known peptides, wherein an expanded peptide is creatively designed to additionally interact with charged amino acids of D420 and K458, located at the rear side of the known binding boundary between RBD and hACE2. The peptide of the present invention exhibits high possibility as a therapeutic agent for COVID-19.

Systems and methods are provided that allow for the determination and prediction of payload toxicity in therapeutic viruses. This document discloses methods for determining the payload toxicity of peptides expressed in cells, comprising: generating or obtaining multiple expression vectors, each containing a different recombinant nucleic acid sequence encoding a corresponding recombinant peptide; expressing the recombinant nucleic acid sequence in multiple host cells while culturing these host cells; sequencing the multiple expression vectors after culturing the host cells; and correlating at least a portion of the recombinant nucleic acid sequence with a toxicity metric.

The invention provides preparation and application of a monoclonal antibody for diagnosis aiming at a human neutrophil lipocalin (HNL) neoepitope. Two new HNL protein conformational epitopes and a new HNL linear epitope are designed and provided, and the anti-HNL antibody which is combined with the new epitopes and has higher binding affinity and better binding specificity is obtained through screening. The anti-HNL antibody disclosed by the invention can be used for preparing an HNL detection reagent and a kit, has higher sensitivity and specificity when being used for detecting HNL protein in a sample, and can be applied to distinguishing bacterial infection and virus infection.

Methods and compositions are provided herein whereby a patient with cancer is administered a treatment comprising NK cells in order to induce expression of MHC-I in a tumor, and wherein subsequent treatment with T cells effectively targets tumor associated antigens and neoepitopes presented by newly expressed MHC-I in said tumor cells.

To provide a method for treating cancer in an individual.SOLUTION: Methods of administering PD-1 axes binding antagonists (such as anti-PD-1 antibodies or anti-PD - L1 antibodies) and RNA vaccines (e.g., personalized cancer vaccines comprising one or more polynucleotides encoding one or more neo-epitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from an individual) to an individual are provided.SELECTED DRAWING: Figure 1

The present invention relates to a lentiviral vector, in particular a non-integrative lentiviral vector, encoding a KRAS1-23 N-terminal segment, said KRAS1-23 N-terminal segment comprising at least one amino acid substitution in position 12 or 13, in particular in position 12, compared to the amino acid sequence set forth as SEQ ID NO: 1 It further relates to lentiviral vector particle, an isolated cell or a pharmaceutical composition comprising a lentiviral vector according to the invention. The invention further provides a combinatory treatment comprising at least one lentiviral vector, a lentiviral vector particle, an isolated cell or a pharmaceutical composition according to the invention, and at least one chemotherapy agent or treatment and / or at least one immunotherapy agent or treatment. Finally, the invention provides any of the above for their use in the treatment and / or prevention of cancers, in particular of cancers wherein the KRAS1-23 N-terminal segment is mutated.