251 results about "HIV Positivity" patented technology

This invention belongs to the field of biodetection technology, specifically relating to a monoclonal antibody 1D3 for detecting porcine epidemic diarrhea virus (PEDV) and its applications. Its heavy chain variable region CDR sequences are SEQ ID NO. 1-3, and its light chain variable region CDR sequences are SEQ ID NO. 4-6. This antibody specifically recognizes the PEDV / S1 protein, and its binding can be competitively blocked by PEDV-specific neutralizing antibodies in serum, making it suitable for establishing a blocking ELISA method. Detection tools based on this antibody exhibit high specificity and sensitivity, with blocking rates exceeding 50% against PEDV-positive serum. This invention can be used to prepare detection kits or evaluate vaccine immunization efficacy, providing an efficient and accurate technical means for PEDV infection diagnosis and immune monitoring.

The invention discloses an anti-CLDN6 nano antibody and related application thereof, and relates to the field of antibodies. The invention provides an anti-CLDN6 nano antibody, which comprises HCDR1, HCDR2 and HCDR3 in a heavy chain variable region of which the amino acid sequence is as shown in SEQ ID NO: 4, the nano antibody has excellent antigen binding activity, high specificity and good affinity, has relatively strong killing activity on cells with high expression of CLDN6, and can be used for preparing anti-CLDN6 drugs. The requirements of CLDN6 positive tumor immunotherapy on efficient, specific and high-penetrability antibody molecules are met, and a new strategy and means are provided for tumor therapy.

The invention provides bovine ephemeral fever virus positive serum as well as a preparation method and application thereof. The preparation method comprises the following steps: culturing bovine ephemeral fever virus by using MDBK suspension cells, inactivating by using beta-propiolactone, concentrating by using a 500kd hollow fiber column to obtain an antigen solution, and emulsifying the antigen solution and 61VG adjuvant according to a mass ratio of 1: 1.5 to prepare the vaccine; carrying out primary immunization and secondary immunization on the receptor, collecting blood of which the serum neutralizing antibody titer is greater than 1: 4096 14-21 days after the secondary immunization, and separating to obtain positive serum. The positive serum can be used for specific test, identification test and the like of the bovine ephemeral fever virus, can also be used for preparing related reagents, kits and standard substances, and provides efficient and normative technical support for prevention and control of bovine ephemeral fever.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

Provided herein are compositions, methods, and uses involving anti-Mucin-16 (MUC16) agents that immunospecifically bind an epitope of Mucin-16 (MUC16). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer and diseases associated with positive MUC16 expression.

The invention provides a nucleic acid probe, a primer group, a kit, a detection method and application, and relates to the technical field of biology. The nucleotide sequence of the nucleic acid probe is as shown in SEQ ID NO. 1; wherein the 3'end of the nucleic acid probe is modified with MGB, and locked nucleic acid is modified at a base position corresponding to the difference between the swine fever wild strain and the swine fever vaccine strain in the nucleotide sequence. According to the nucleic acid probe, a specific sequence is utilized to precisely target a swine fever wild strain, and locked nucleic acid modification is introduced at a differential site, so that the recognition capability on single-base mismatch is remarkably enhanced, non-specific binding to a vaccine strain is thoroughly blocked, and false positive interference is eliminated; and 3 '-terminal MGB modification is matched to improve the binding stability and sensitivity, so that the efficient and accurate identification of the swine fever wild strain under the immune background is ensured.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention discloses a preparation method and application of a cat main allergen FEL-1 nano antibody FEL-1-Nb, and relates to the technical field of antibody preparation, and the preparation method comprises the following steps: preparing an immunogen; animal immunization and library construction; constructing and panning a phage display library; screening and identifying positive clone; and expression and purification of the nano antibody: cloning the positively cloned VHH gene to an expression vector such as a pET series, transforming an expression strain such as escherichia coli BL21 (DE3), carrying out IPTG induced expression, and purifying through an inclusion body purification method to obtain a high-purity nano antibody protein. The nano antibody FEL-1-Nb provided by the invention can be specifically bound with a cat main allergen FEL-1 protein, the unique amino acid sequence of the nano antibody FEL-1-Nb is shown as SEQIDNO: 1, high-affinity binding with the FEL-1 protein is ensured, the positive clone binding rate is high through phage display panning and ELISA verification, the phage recovery rate after the third round of panning is increased by more than 1000 times compared with the first round of panning, and the positive clone binding rate is higher than that of the first round of panning. Therefore, the nano antibody has excellent targeted recognition capability.

The invention belongs to the field of biological immunity, and discloses a linear B cell epitope of African swine fever virus NP419L protein and application. The epitope sequence shows good immunoreactivity through ASFV positive pig serum recognition verification. The African swine fever positive serum can be identified by using the B cell epitope identified by the invention to carry out ELISA (Enzyme-Linked Immunosorbent Assay) experiment, and the sensitivity of the African swine fever positive serum is superior to that of NP419L protein full length and other truncated fragments. The epitope identified by the invention has high conservative property in reference ASFV strains in a plurality of popular regions in China, and has wide universality and adaptability. The kit can be widely applied to etiological diagnosis, serological diagnosis, immunological detection and disease prevention and treatment of African swine fever viruses, and can be applied to preparation of African swine fever vaccines, pathogenesis research and the like.

The application discloses a kind of 2-substituted benzylhydrazine-4-indole pyrimidine-5-carbonitrile derivatives and preparation method and application thereof.The derivative has general formula (I) structure: wherein R is hydroxyl or C1-C4 alkoxy, n=1~3.Preferred compound is 2-hydroxy, 4-hydroxy-3-methoxy, 2,3-dihydroxy or 2,4-dihydroxy substituted benzylhydrazine derivative.The application also provides key intermediate 2-hydrazine-4-(1H-indole-3-carbonyl) pyrimidine-5-carbonitrile and preparation method thereof.In vitro antitumor activity shows that the derivative has excellent inhibitory activity on human gastric cancer cell MGC-803, and the inhibition rate is up to 96.3% at 10 μmol / L, which is better than positive control doxorubicin.In vivo combination test shows synergistic effect with 5-fluorouracil or anti-PD-1 antibody.The compound of the application has mild synthesis route, high yield, various preparation forms, good safety, and can be applied in the preparation of anti-gastric cancer drugs.

The invention relates to a primer-probe set, comprising a forward primer having the nucleotide sequence of SEQ ID NO:1 and a reverse primer having the nucleotide sequence of SEQ ID NO:2, and a peptide nucleic acid (PNA) probe having the sequence of HEX-OO-(SEQ ID NO:3)-Lysine-BHQ1, which are used for differentiating the Peste des Petits Ruminants (PPR) virus vaccine and field strains and for preventing false positive results arising from the PPR vaccine, as well as to their operating temperatures. Said primer-probe set can differentiate between the vaccine strain containing the nucleotide sequence of SEQ ID NO:4 and the field strain containing the nucleotide sequence of SEQ ID NO:5. Thus, by means of said primer-probe set, false positive results arising from the PPR vaccine are prevented, and accordingly, unnecessary quarantine measures are also avoided.

The application belongs to the technical field of biology and particularly relates to an ELISA kit for detecting chicken astrovirus type II antibodies and a preparation method. The Cell-ELISA experiment is carried out by using LMH cells infected with chicken astrovirus type II to detect the chicken astrovirus type II antibodies. The method has no cross reactivity with positive serum of Newcastle disease virus, avian influenza virus, chicken infectious anemia virus, avian leukosis virus, Marek's virus and chicken infectious bursal virus, which indicates that the method has good specificity. The Cell-ELISA method is used to detect the chicken serum sample to be detected by using whole virus infection, and is assembled into a kit for measuring chicken astrovirus antibodies in serum. The kit can be used for serological diagnosis of chicken astrovirus type II infection, monitoring of the level of antibodies, epidemiological investigation and the like, and provides a novel and effective detection means for prevention and treatment of chicken astrovirus type II.

This invention provides a kit for detecting anti-peroxidase-1-IgG antibodies, comprising the antigen protein peroxiredoxin-1 (peroxidase-1), a solid-phase carrier, labeled antibody, antigen dilution buffer, sample dilution buffer, antibody dilution buffer, substrate chromogenic agent, washing buffer, standards, positive control, and negative control. This kit utilizes an indirect reaction principle combined with magnetic microparticle chemiluminescence immunoassay to detect anti-peroxidase-1-IgG antibodies in the serum of the test sample. This invention is the first to identify autoantibodies against the target antigen peroxidase-1 in the serum of patients with autoimmune nephrotic syndrome. The provided kit provides a basis for domestic and international research on the molecular mechanisms and clinical diagnosis and treatment of autoimmune nephrotic syndrome related to peroxidase-1 and peroxidase-1-IgG autoantibodies.

The invention relates to the technical field of molecular generation, and discloses a reverse design method using a molecular spectrum as a medium to be applied to virus protein drug molecules, which comprises the following steps: firstly, constructing a data set containing a molecular SMILES identifier and a corresponding molecular spectrum, and carrying out drug-likeness and false positive preliminary screening on compounds by adopting Lipinski five rules and a PAINS mode; then training a conditional diffusion model, and generating a target molecular spectrum by taking specific drug properties as conditions; the spectrum is mapped into a molecular SMILES structure through a Transform decoder, so that accurate conversion from the spectrum to the molecule is realized; finally, through conformation optimization and stability verification, candidate drug molecules meeting specific treatment requirements are output. The method effectively avoids the invalid structure problem caused by cross-dimension generation, significantly improves the synthesizability and patent medicine potential of generated molecules, and is suitable for efficient molecular design of antiviral drugs, inhibitors and the like.

The invention belongs to the technical field of antibody preparation, and particularly relates to an anti-terminal deoxynucleotidyl transferase (TdT) antibody and application thereof. The amino acid sequences of CDR1-3 on a light chain variable region of the antibody are respectively shown as SEQ ID NO.3-5, and the amino acid sequences of CDR1-3 on a heavy chain variable region of the antibody are respectively shown as SEQ ID NO.8-10. The antibody disclosed by the invention can specifically recognize TdT protein naturally expressed in cells and tissues, has the advantages of high specificity, high affinity, high sensitivity and the like when being used for immunoblotting, immunohistochemistry and other immunodetection systems, is beneficial to reducing false positive and false negative rates in pathological diagnosis, improves the accuracy of immunodiagnosis, and has a good application prospect. The method has wide application potential in the field of immunological detection of living biological samples. In addition, the antibody disclosed by the invention has cross-species reaction characteristics on homologous TdT proteins of human, mice and rats, so that the application scene of the antibody is greatly expanded.

A method of determining a therapeutic regimen in a patient with cancer comprising determining in a sample from the patient the tumor mutation burden (TMB) and loss of heterozygosity (LOH), wherein high TMB in combination with no LOH is indicative of a positive outcome when treated with a checkpoint inhibitor and high TMB with LOH is indicative of a poor outcome, is provided herein.

The present application relates to an antibody-drug conjugate, a method for producing the same, and uses thereof. Specifically, the present application relates to an antibody-drug conjugate for use in treating B7-H3-positive tumors. The antibody-drug conjugate of the present application comprises a B7-H3 antibody, which has excellent binding activity to B7-H3-positive cells and can efficiently transport drugs to B7-H3-positive cells. The antibody-drug conjugate of the present application has an excellent drug-antibody binding ratio and exhibits excellent targeted killing effects against tumors such as lung cancer, breast cancer, gastric cancer, and colon cancer. Therefore, the present application further provides a method for producing the antibody-drug conjugate and its use in treating B7-H3-positive tumors.

The invention discloses a double-target chimeric antigen receptor capable of simultaneously targeting TLL1 and B7H3, a CAR-T cell and application of the double-target chimeric antigen receptor. The chimeric antigen receptor is a fusion protein which is sequentially composed of Omburt-scFv (SEQ ID NO: 1) targeting B7H3, a CD8 alpha hinge region and transmembrane region, a 4-1BB costimulatory domain, a CD3 zeta signal domain and TLL1-scFv (SEQ ID NO: 6) targeting TLL1 from an N terminal to a C terminal. The TLL1-scFv can be efficiently combined with TLL1 protein, can inhibit a TGF-beta signal channel and block prostate cancer cell migration, and is integrated into CAR of targeted B7H3, so that the double-target CAR-T cell with direct killing and immune microenvironment regulation functions is successfully constructed. The CAR-T cell has a remarkable killing effect on a prostate cancer cell line DU145, can be strongly activated after being co-cultured with a target cell and secretes a large amount of IFN-gamma and TNF-alpha, and shows high immunocompetence. The invention provides a new synergistic immunotherapy strategy for the B7H3-positive prostate cancer with the TGF-beta signal channel activated.

Provided are bispecific antibody-drug conjugates targeting EGFR and HER3, pharmaceutical compositions comprising the conjugates, their use for treating or preventing diseases or conditions associated with EGFR and / or HER3 activity, particularly EGFR and / or HER3-positive tumors, and their use in the preparation of pharmaceuticals for treating or preventing diseases or conditions associated with EGFR and / or HER3 activity, particularly EGFR and / or HER3-positive tumors.

The present disclosure relates to human antibodies specific to dermatomyositis antigen peptides, preparation methods and uses. Specifically, the present disclosure relates to a monoclonal antibody that specifically binds to MDA5 antigen protein, a preparation method of the monoclonal antibody and a use of the aforementioned monoclonal antibody in the preparation of a drug for the diagnosis, prevention or treatment of inflammatory myopathy or its complications. The antibody or antigen-binding fragment against MDA5 screened by the present disclosure specifically binds to MDA5 antigen, can be used as a reference standard for qualitative detection of MDA5 positivity, realizes qualitative or quantitative detection of the level of anti-MDA5 autoantibody in patients with inflammatory myopathy or its complications, and has important significance for the clinical diagnosis, disease monitoring and treatment of patients with DM, CAMD, DM-ILD, CADM-ILD and the like.

The invention relates to a method for detecting activation of specific T cells after tuberculosis infection and application of the method. Specifically, the invention provides a reagent combination for detection, and the reagent combination comprises an anti-CD4 antibody (CD4 antibody), an anti-CD154 antibody (CD154 antibody), an IFN-gamma detection antibody and a tuberculosis specific antigen. According to the method, through peripheral whole blood collection, PBMC cell separation, T cell activation (activation), activation termination (blocking), antibody labeling, membrane rupture, fixation, intracellular cytokine dyeing, flow cytometry detection and result analysis and judgment, the ratio of the expression IFN-gamma cells in the CD4 + CD154 + cells can be rapidly and accurately determined, and by combining an ROC curve and a constructed judgment standard, the content of the IFN-gamma cells in the CD4 + CD154 + cells can be determined, and the content of the IFN-gamma cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells in the CD4 + CD154 + cells can be determined. And the sample to be detected is judged to be in a positive / negative / gray region, so that whether a patient is infected by the mycobacterium tuberculosis or not can be more accurately diagnosed, especially aiming at a whole blood sample from a special crowd.

The invention belongs to the technical field of biological medicine and disease prevention and treatment, and particularly relates to an SSEA4 conjugated virus-like particle anti-cancer vaccine as well as a preparation method and application thereof. Specifically, according to the vaccine, an SSEA4 antigen is efficiently synthesized through a chemical enzyme method, then the SSEA4 antigen is covalently coupled with a virus-like particle (VLP), the SSEA4 antigen and the VLP are combined with a monophosphoryl lipid A adjuvant with high safety, an organism can be induced to generate strong and lasting SSEA4-resistant humoral immune response, the generated antibody can specifically recognize and kill SSEA4 positive tumor cells, and the SSEA4 positive tumor cells can be effectively killed. Meanwhile, good safety is shown in an animal model, a new solution is provided for immunotherapy of SSEA4 positive tumors, and therefore the SSEA4 positive tumor immunotherapy polypeptide has wide application prospects and market value.

The invention belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting PD-L1 cross binding of human and cynomolgus monkeys and application of the single-domain antibody. The single-domain antibody disclosed by the invention has the specificity of resisting PD-L1 of human and cynomolgus monkeys, and shows relatively strong binding efficacy in the binding detection of PD-L1 target protein or PD-L1 overexpression cells; in the detection of blocking PD-1 / PD-L1 functions, a part of the single-domain antibodies even show a blocking effect which is obviously superior to that of Atezolizumab, so that the single-domain antibodies prepared by the invention can be used for diagnosis, treatment and prognosis detection of PD-L1 positive tumors. Meanwhile, the single-domain antibody disclosed by the invention has cross-species cross binding capacity, can be directly used for preclinical pharmacodynamics and safety evaluation, does not need to develop a species-specific substitution antibody, and realizes'one target and double effects'.

The invention provides an anti-FOLR1 nano antibody and related application thereof, and relates to the technical field of biological medicines. The nano antibody can be combined with an FOLR1 antigen with high affinity and specificity. An in-vitro experiment verifies that the FOLR1-CD3 bispecific antibody constructed on the basis of the FOLR1-CD3 bispecific antibody shows remarkable killing activity on various FOLR1 positive tumor cells, can be used for treating cancers and other diseases related to FOLR1 expression, and provides an important basis for developing an immunotherapy strategy with efficient and lasting anti-tumor activity.

A provided self-replicating mRNA is transcribed from an alphavirus backbone vector. The alphavirus backbone vector comprises gene sequences of alphavirus non-structural proteins nsP2, nsP3, nsP4, and mutated nsP1. A cysteine at position 492 of the mutated nsP1 is mutated into serine. The self-replicating mRNA has a higher expression level and a longer expression time for a target gene. The self-replicating mRNA is used for expressing IMP3, and can be prepared into a vaccine having good preventive and therapeutic effects on IMP3-positive tumors. Therefore, the present invention has good application prospects in drug and vaccine development.

The invention relates to the fields of molecular biology and virology, and provides a method for preparing a specific MHC haplotype-derived cell-binding virus. The method comprises the following steps: firstly, obtaining chick embryos of different haplotypes, separating CEF cells, transiently expressing exogenous fluorescent protein through electrotransfection, then carrying out virus inoculation, carrying out flow sorting to obtain a fluorescent positive cell population carrying MDV, and carrying out quantitative analysis on the cell population to obtain the specific MHC haplotype chicken Marek's Disease Virus (MDV), thereby obtaining the specific MHC haplotype chicken Marek's Disease Virus Marek's Disease Virus Marek's Disease Virus Marek's Disease Virus. And carrying out in-vitro propagation to obtain the purified MDV with a specific haplotype source. The purified virus can provide a test material for related research of haplotype on virus infection, and can be widely applied to in-vitro purification of different cell binding viruses and related research of specific MHC molecule presenting virus peptides. The method disclosed by the invention is beneficial to carrying out related research aiming at the host immune response of the virus and analyzing the hereditary basis of haplotype to MDV differential resistance, and is expected to be applied to preparation of vaccine virus.

The application discloses a triple fluorescent quantitative PCR detection kit for simultaneously detecting CHIKV, BFV and RRV, which contains a specific primer probe composition for simultaneously detecting chikungunya virus, Barmah Forest virus and Ross River virus, can simultaneously detect three viruses which are transmitted by insect vectors and cause acute fever with arthralgia symptoms in human beings in one PCR reaction tube, and has excellent specificity and repeatability, and is suitable for routine laboratory diagnosis of suspected samples of alphavirus infection, and provides a rapid and accurate detection method for the epidemiological study of CHIKV, BFV and RRV.

The present application provides a human FGFR2 antibody and application thereof. Specifically, the present application discloses an antibody specifically binding to human FGFR2, which has higher selective binding to FGFR2b subtype, and weaker binding to other subtypes such as FGFR2c, and has strong killing activity to tumor cells endogenously expressing FGFR2b such as KATOIII and SNU-16, and can be used for developing drugs and diagnostic reagents for treating FGFR2b positive tumors.

A system for binding peptide search for immunotherapy is presented. The system includes employing a deep neural network to predict a peptide presentation given Major Histocompatibility Complex allele sequences and peptide sequences, training a Variational Autoencoder (VAE) to reconstruct peptides by converting the peptide sequences into continuous embedding vectors, running a Monte Carlo Tree Search to generate a first set of positive peptide vaccine candidates, running a Bayesian Optimization search with the trained VAE and a Backpropagation search with the trained VAE to generate a second set of positive peptide vaccine candidates, using a sampling from a Position Weight Matrix (sPWM) to generate a third set of positive peptide vaccine candidates, screening and merging the first, second, and third sets of positive peptide vaccine candidates, and outputting qualified peptides for immunotherapy from the screened and merged sets of positive peptide vaccine candidates to support downstream clinical decision making.