381 results about "Tumor specific" patented technology

The invention discloses a modified Trim 21 (delta Trim 21)-based target protein degradation control system, which takes a modified protein delta Trim 21 degradation system as a basis, takes blue light, abscisic acid, Danoprevir and / or MK-5172 as inductors, controls the combination of target protein and delta Trim 21 by introducing and modifying a controllable protein dimerization system on the basis of the modified protein delta Trim 21 degradation system, and improves the target protein degradation control system. The protein targeted degradation capable of being modularly regulated and controlled is carried out. Two regulation and control modules, namely a target protein recognition module and a degradation module based on E3 ubiquitinase, are constructed by splitting and recombining a controllable protein dimerization system and a delta Trim 21 structural domain. The invention also discloses a degradation device comprising the system. The invention also discloses a method for accurately regulating endogenous proteins (degradation of proteins related to tumorigenesis) by using the programmable regulation type modular protein degradation device, so as to achieve the effect of specifically killing tumors. The invention also provides a eukaryotic expression vector and a regulation method of the programmable regulation type protein targeted degradation device.

The invention belongs to the technical field of molecular biomedicine, and provides a colorectal cancer early screening method based on multi-omics sequencing, which comprises the following steps: collecting a plasma sample to be detected, collecting sequencing data to be detected, and classifying a colorectal tumor early screening model. The training process of the colorectal tumor early screening model comprises the steps of original sequencing data acquisition, quality control and human reference genome comparison, reference methylation data acquisition, tumor specific region screening, plasma cfDNA sequencing data acquisition, coordinate determination sequencing data acquisition, methylation feature set screening and terminal motif feature screening. And carrying out breakpoint motif feature screening, feature merging and model training. By constructing the colorectal tumor early screening model, the non-invasive colorectal cancer detection method with high cost effectiveness is realized, the economic cost of sequencing is reduced, and the accuracy and sensitivity of detection are remarkably improved.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

The invention provides a tumor cell vaccine as well as a preparation method and application thereof. The preparation method comprises the following steps: acquiring and culturing tumor cells; enabling the cell membrane of the tumor cell to express a targeting antibody by utilizing a gene vector infection or gene editing technology, and enabling the targeting antibody to be used for enabling the tumor vaccine to be combined with the dendritic cell; performing overexpression of tumor specific protein on the cell membrane surface of the tumor cell by using a gene vector infection or gene editing technology; a nucleic acid substance of a target protein is wrapped by lipid nanoparticles to form a vaccine framework, and the nucleic acid substance can enable target cells to express directional chemotactic molecules; wherein the directed chemotactic molecule is used for transferring the dendritic cells to lymph nodes; the target vaccine is obtained by wrapping the vaccine framework with the cell membranes of the tumor cells, lymph node homing of the dendritic cells can be promoted, and the antigen presentation efficiency is increased and the immune effect is enhanced through tumor specific protein carried by the target vaccine and assisted by an immunologic adjuvant.

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.

The invention relates to the technical field of nano-drug presentation systems, in particular to a TCR (T cell receptor) nano-vesicle antibody with both T cell redirection and immunosuppression reversal as well as a preparation method and application of the TCR nano-vesicle antibody. The TCR nano-vesicle antibody comprises a vesicle formed by a liposome and a cell membrane; tCR protein, a PD-1 antibody and a CD3 antibody are loaded on the vesicles. The nano vesicle antibody has the functions of T cell redirection and immunosuppression reversion; the difficulty of low stability of the soluble TCR is overcome; the polypeptide can be rapidly enriched in tumor tissues through tumor specificity TCR, and CD8 + T cells infiltrated by tumors are directly activated through an anti-CD3 antibody; depletion of T cells can be reversed through the PD-1 antibody on the surface, and the effector function of tumor infiltration CD8 + T cells is improved. The technical scheme can solve the technical problems that the TCR stability is not ideal and the immunosuppression state of the tumor microenvironment is difficult to overcome, and has ideal application and popularization prospects.

The invention belongs to the technical field of biological medicines, and particularly relates to an antigen peptide library for inducing tumor specific immune response, the antigen peptide library comprises eight antigen peptides, and the amino acid sequences of the eight antigen peptides are respectively shown as SEQ ID NO.1-SEQ ID NO.8. The invention further discloses a preparation method of the antigen peptide library. The antigen peptide has high immunogenicity and can effectively stimulate and induce generation of specific cytotoxic T lymphocytes when being loaded on antigen presenting cells, in-vitro killing experiments show that CTL cells induced and activated by loading new antigen DC have a high tumor killing effect, and the cell killing activity of the CTL cells is 90% or above. When model mice are treated by adoptive T cell back-transfusion of CTL cells induced by the new antigen peptide library, the tumor volume can be effectively reduced, the survival rate of the tumor can be remarkably increased, and good treatment potential is achieved.

The invention discloses an anti-tumor drug delivery system based on click chemistry and a hollow covalent organic framework material as well as a preparation method and application of the anti-tumor drug delivery system, and belongs to the technical field of novel biomedical materials. The anti-tumor drug delivery system based on the click chemistry and the hollow covalent organic framework material comprises a bowl-shaped hollow covalent organic framework material carrier, and a click chemistry prodrug 1 and a click chemistry prodrug 2 which are loaded in the bowl-shaped hollow covalent organic framework material carrier, the click chemistry prodrug 1 is a compound containing an aldehyde group, and the click chemistry prodrug 2 is a compound containing an amino group. By combining the high-specificity reaction of click chemistry with the excellent drug loading performance of HCOF, accurate drug release can be realized in a tumor-specific microenvironment, the toxicity of normal cells can be remarkably reduced, the treatment effect is improved, and a wide clinical application prospect is shown.

The invention discloses a polypeptide-based PROTAC condensation body as well as a preparation method and application of the polypeptide-based PROTAC condensation body. The polypeptide-based PROTAC aggregate comprises an HER2 (human epidermal growth factor receptor) targeting module, an EGFR (epidermal growth factor receptor) targeting module, a VHL E3 ligase targeting module and a self-assembly module. The polypeptide-based PROTAC condensation body can dynamically enrich E3 ligase VHL and promote efficient ubiquitination degradation of HER2, EGFR and downstream signal channel protein of HER2 and EGFR, the degradation efficiency of HER2 and EGFR protein can reach 92%, the degradation efficiency of downstream signal channel protein such as SOS2 and RAS can reach 80%, and in addition, the polypeptide-based PROTAC condensation body has the advantages that the polypeptide-based PROTAC condensation body can be used as an efficient ubiquitination condensation body; the polypeptide-based PROTAC condensation body has the characteristics of tumor targeting and long-acting retention, and dose-dependent tumor specific accumulation and retention can be realized through in-situ self-assembly.

The present disclosure provides a composition comprising a nucleic acid sequence encoding from about 1 to about 100 amino acid sequences, the amino acid sequences being tumor-specific antigens wherein at least one tumor-specific antigen is an amino acid sequence associated with the WNT pathway. In some embodiments, the nucleic acid sequence encodes from about 20 to about 60 tumor specific antigens; wherein from about 1 to about 8 tumor specific antigens are selected from one or a combination of the following: WNT, CTNNB1, AXIN1, AXIN2, APC, CK1, and GSK3B. Also provided is a cell comprising any one or more compositions disclosed herein and a pharmaceutical composition comprising: (i) a therapeutically effective amount of one or more compositions as disclosed herein; and (ii) a pharmaceutically acceptable carrier. A method of treating cancer in a subject in need thereof is also provided.

The invention relates to the field of cells, in particular to a cytokine combination, a culture medium, a tumor-specific T cell population and application thereof. The preparation method comprises the following steps: firstly, activating a solidified CD3 monoclonal antibody, enabling T cells to automatically secrete part of cell factors, and meanwhile, enabling mononuclear cells in peripheral blood lymphocytes to be mature into dendritic cells under the action of adding exogenous cell factors; adding non-activated peripheral blood lymphocytes again, and activating and proliferating T cells under the action of dendritic cells and cell factors; then, activation and proliferation of T cells are further promoted, so that a tumor specific T cell population is obtained, and the T cell population can directly kill tumors and inhibit the growth of the tumors.

The invention provides a puncture sample detection platform based on a tumor protein targeting probe. According to the puncture sample detection platform, IR-780 is used for marking tumor specific protein in a puncture sample; the improved three-dimensional gel electrophoresis device is used for separating proteins in tissues; the gel processing platform is used for processing and analyzing the separation gel medium; and the automatic diagnosis platform is used for automatically judging benign and malignant conditions of the puncture sample according to the intensity and coherence of the fluorescence signal and circling the contour of the malignant sample. Compared with clinical pathological examination, the method has the advantages that benign and malignant puncture samples are judged by evaluating the protein content of various tumor receptors, and the problem of diagnosis difficulty caused by limited histological information is well solved. Meanwhile, the dependence on visual diagnosis of pathological analysis of the frozen section and experience of pathologists is reduced, and the accuracy and efficiency of pathological tissue diagnosis are effectively improved. The automatic diagnosis platform can eliminate a large number of benign samples and can reduce repeated work of pathologists.

The invention provides a preparation method of DC cells. The preparation method is especially suitable for rapidly obtaining high-purity and high-functional-activity DC cells. The method comprises the steps of separation from peripheral blood mononuclear cells (PBMC), induction culture, maturation treatment and the like, maturation of the dendritic cells is promoted by introducing an anti-CD47 single-domain antibody or LPS, and the immunocompetence of the dendritic cells is remarkably improved. The method is further applied to preparation of an anti-tumor cell preparation, the capability of activating tumor specific T cells by tumor antigen-loaded DC cells can be remarkably enhanced, and the killing activity of the T cells to tumor cells is improved. The preparation method provided by the invention overcomes the defects in the prior art, has the advantages of high efficiency, safety and stability, and can provide a more reliable cell therapy scheme for tumor immunotherapy.

The invention relates to an immune sensitization IRE treatment platform based on NK cell membrane coated manganese carbonate. A manganese carbonate composite nano material is formed by coating the surfaces of manganese carbonate nano particles with cell membranes. According to the invention, higher tumor specificity enrichment is realized, non-target tissue accumulation and systemic toxicity risks are reduced, collaborative integration of tumor targeted delivery, immune activation and IRE ablation is realized, and compared with single IRE, anti-tumor immune response is significantly enhanced.

The invention provides a compound for releasing a urine fluorescent biomarker under induction of mitochondrial DNA mutation as well as a preparation method and application of the compound, and belongs to the technical field of medicines. The compound disclosed by the invention is prepared by the following steps: complementarily pairing a hybrid nucleic acid nano-carrier containing single-stranded DNA (Deoxyribose Nucleic Acid), an annular fluorescent reporter molecule and a Cas12a / crRNA compound through bases of DNA or RNA, and then coating polyethyleneimine and hyaluronic acid. A CRISPR / Cas12a system is selected as a converter of tumor specific mitochondrial DNA mutation information and urine fluorescence signals, a nano delivery system which responds to mtDNA single base mutation and is used for tumor progress monitoring and early metastasis warning is designed and synthesized, and the nano delivery system has a good application prospect in tumor progress monitoring and early metastasis sensitive detection.

The invention belongs to the technical field of biological medicines, and particularly relates to a recombinant oncolytic herpesvirus and application thereof. In order to solve the problems of insufficient replication efficiency, limited immune activation and the like of the existing oncolytic herpesvirus, the invention provides a recombinant oncolytic herpesvirus which contains a coding neurotoxic factor regulated by a tumor specific promoter or a gene related to replication and a gene segment for coding an immunomodulatory factor. Experiments prove that the recombinant oncolytic herpesvirus prepared by the invention has multiple advantages of high replication efficiency, strong tumor targeting, remarkable treatment effect on various tumors, high safety and the like, provides a brand new drug development thought and treatment choice for the field of tumor immunotherapy, and has important clinical application value and market prospect.

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.

Methods for detecting a tumor using a sample in which tumor DNA fragments are present only in a very low concentration, beyond the statistical limit of detection, where methods include: obtaining sequence data for tumor nucleic acid from a tumor from a subject and analyzing the sequence data to identify a plurality of tumor-specific variants that are in the tumor nucleic acid and that are not in non-tumor nucleic acid of the subject; selecting a marker variant that appears duplicated in tumor nucleic acid (compared to non-tumor nucleic acid) a greater number of times than other ones of the tumor variants; performing an assay to detect the marker variant in a sample from the subject; and reporting the presence of the tumor in the subject when the assay is positive for the marker variant in the sample.

The invention relates to the technical field of biological medicine, in particular to a nano antibody conjugate as well as a preparation method and application thereof. The nano antibody conjugate comprises coupled antibody fusion protein and bortezomib; the antibody fusion protein is a fusion protein of elastin-like polypeptide and an anti-Her2 nano antibody. The nanometer antibody conjugate can improve the stability and enzyme selectivity of bortezomib and reduce the toxic and side effects of drugs, meanwhile, the tumor targeting effect is achieved by combining a tumor specific nanometer antibody targeting technology, and the nanometer antibody conjugate can be used for treating Her2 high-expression cancers and has excellent application and popularization value and potential.

Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor.

The invention discloses a CT image whole-body multi-tumor segmentation method, which comprises the following steps: firstly, preprocessing collected CT images of multiple parts and multiple types of tumors, then inputting the preprocessed images into a pre-trained organ segmentation model, and obtaining segmentation results of different organs and local tumor images of different parts; thirdly, extracting and fusing features by utilizing global and local tumor segmentation models, and enhancing extraction of tumor specific features by taking an organ segmentation result as guide information and combining tumor text prompts generated by a large language model; and finally, carrying out step-by-step up-sampling through a decoder to obtain an accurate tumor segmentation image. According to the invention, global and local features are integrated, and an organ segmentation result is used as guidance to form a position attention module, so that the adaptability of the model to different organ tumors is enhanced; through a tumor text prompt driving mechanism of a large language model, specific hyper-parameters for each tumor are generated, and the accuracy and robustness of the model in a multi-part and multi-type tumor segmentation task are improved.

The invention relates to application of PWWP2B as a target spot in preparation of leukemia treatment drugs, and belongs to the technical field of biological medicines. In order to solve the problem that a traditional AML treatment target is lack of tumor specificity and is difficult to meet clinical requirements, the invention provides application of PWWP2B as a target in preparation of leukemia treatment drugs. The invention proves that PWWP2B is highly expressed in acute myelogenous leukemia cells, and the PWWP2B as a molecular marker can accurately distinguish acute myelogenous leukemia from normal healthy people or non-leukemia patients. In-vivo and in-vitro experiments prove that by knocking out PWWP2B, proliferation and clone formation of acute myelogenous leukemia cells can be remarkably inhibited, differentiation and apoptosis of the acute myelogenous leukemia cells are promoted, and activity of leukemia cells in a patient body is inhibited. The invention discloses the new application of the small molecule compound EZM0414 in treating acute myelogenous leukemia for the first time, and the synergistic interaction of the small molecule compound EZM0414 and a methylase inhibitor can be realized.

The invention discloses a ternary carrier-free nanoparticle as well as a preparation method and application thereof. The ternary carrier-free nanoparticles comprise nanoparticles which are formed by the chlorine e6, the lonidamine and the RG108 through an intermolecular interaction force. The nanoparticles can improve effective absorption and accumulation of drugs in tumors, can induce tumor specific pyroptosis and immunogenic effect under laser irradiation, and can promote maturation of antigen presenting cells and recruitment and activation of cytotoxic T lymphocytes, thereby starting adaptive anti-tumor immunity.

A system and method for generation and use of radiation outcome prediction (response & side effects) score for patients undergoing radiotherapy for various medical conditions wherein the score is a personalized score, provided by analyzing multiple parameters including the tumor specific, patient specific, gene specific and treatment planning specific parameter(s), during and post therapy.

Breast cancer is now the most common cancer in the world, and despite treatment progression in decades in the past, metastatic breast cancer is still a disease which cannot be cured. Novel tumor specific antigens (TSA) and tumor associated antigens (TAA) expressed by breast tumor cells are described herein. Synthetic long peptides, nucleic acids, compositions, cells, TCRs, antibodies, and vaccines derived from these TSAs and TAAs are described. The use of the TSA / TAAs, nucleic acids, compositions, antibodies, cells and vaccines for the prevention or treatment of breast cancer, including triple negative breast cancer (TNBC), is also described.

The application relates to the field of biological preparations, and particularly discloses an immunochromatographic reagent for detecting malignant tumors in urine and application thereof, which is used for solving the problems of poor recognition of tumor specific epitopes, heavy background interference, spectrum overlap and high subjectivity of artificial judgment in the single staining and color development of acridine orange in the detection of urinary exfoliative cells of bladder cancer. The color development reagent comprises A reagent, B reagent, C reagent and D reagent. The A reagent is provided with an antibody complex for target antigens of bladder tumor cells in urine exfoliation and acridine orange. The B reagent comprises a fluorescently labeled secondary antibody composition corresponding to the A reagent and an enzyme-labeled secondary antibody-tyramide deposition amplification composition. In the application, AI imaging analysis is adopted to calibrate layered recognition labels and acridine orange staining negative and positive labels. Through multi-target immunochromatography, two sets of color separation amplification schemes and AI imaging analysis, the application improves the recognition ability of bladder tumor specific epitopes, the image quality and the image analysis accuracy in the detection of urinary exfoliative cells.

Provided herein are immortalized mesenchymal stem cells comprising a replicating recombinant retrovirus. Methods for treating a cell proliferative disorder using these immortalized mesenchymal stem cells are also provided.

The present invention provides compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.

This disclosure relates to a technique for identifying tumor-specific mutations through integrated analysis of next-generation sequencing data using machine learning models. In certain embodiments, a computer implementation method is provided, comprising: generating sequence reads from one or more samples collected from the same patient; generating variant calling files by analyzing the sequence reads corresponding to each of the one or more samples; generating a list of candidate somatic variants by comparing the variant calling files; generating a score for each of the candidate somatic variants in the list of candidate somatic variants using a classification machine learning model, wherein the score is generated based on a plurality of classifications generated by the classification machine learning model; determining the ctDNA status for the patient based on the score, wherein the ctDNA status is either positive or negative; and generating a report providing the ctDNA status for the patient.