70 results about "Tumor-Derived" patented technology

The disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer (SCLC) having a high tumor mutational burden (TMB) status comprising administering to the subject a monotherapy comprising an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody. The present disclosure also provides a method for identifying a subject suitable for treatment with an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.

The invention discloses a method and a device for constructing a cancer early screening model based on cfDNA difference statistics. The construction method of the cancer early screening model comprises the following steps: performing difference statistics on tumor-derived cfDNA and healthy individual-derived cfDNA in a low-depth whole-genome sequencing mode, and establishing the cancer early screening model to realize non-invasive early screening of cancers; the difference statistics comprises cfDNA fragment size characteristic difference statistics, cfDNA upstream and downstream continuous three groups of 3bp base combination category distribution frequency change trend difference statistics at a fracture position and sequencing data coverage depth mode difference statistics of the cfDNA near TSS. The method has the advantages of being minimally invasive, high in early diagnosis sensitivity, capable of achieving dynamic monitoring and the like, the limitation of cfDNA gene mutation detection in the early stage of the tumor is overcome, and information lag or deletion caused by tumor heterogeneity is avoided.

The invention discloses application of a tumor-derived acellular extracellular matrix in preparation of a medicine for promoting angiogenesis and tissue regeneration. The invention provides a strategy for regulating and controlling tissue regeneration based on a tumor-derived acellular extracellular matrix microenvironment, a novel angiogenesis promoting biological material is constructed by combining the high similarity of a tumor microenvironment and a regeneration microenvironment such as angiogenesis, and high-efficiency regeneration is realized in various tissue defects. In addition, due to the characteristic of rapid proliferation of the tumor tissue, the productivity bottleneck of a traditional acellular extracellular matrix raw material source is broken through, and sustainable biological raw materials are provided for large-scale production. The method successfully solves the problem that a specific tissue-derived acellular extracellular matrix is difficult to regenerate in a complex damaged microenvironment.

This disclosure provides methods for treating a subject afflicted with a tumor derived from a renal cell carcinoma. The methods comprise administering a first dose to a subject of an anti-PD-1 antibody or antigen-binding portion thereof and / or an anti-PD-L1 antibody or antigen-binding portion thereof, and administering a second dose to the subject, wherein the subject exhibited differential expression in one or more biomarker genes, e.g., CTLA-4, TIGIT, and / or PD-L2, following administration of the first dose.

A rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumor-derived EVs from as little as 1 μL of plasma is described herein. This assay uses binding of gold nanospheres and nanorods with EV- and tumor-derived EV-specificities to produce a local plasmon effect that enhances tumor-derived EV detection sensitivity and specificity. This nPES approach is also a non-invasive method for assessing pancreatic cancer stage and treatment response that can be easily refined for clinical use, and is readily adapted for diagnosis and monitoring of other conditions with disease-specific EV proteins.

Methods for creating a selector of mutated genomic regions and for using the selector set to analyze genetic alterations in a cell-free nucleic acid sample are provided. The methods can be used to measure tumor-derived nucleic acids in a blood sample from a subject and thus to monitor the progression of disease in the subject. The methods can also be used for cancer screening, cancer diagnosis, cancer prognosis, and cancer therapy designation.

The application discloses a separation-free plasma tumor-derived extracellular vesicle detection method, relates to the technical field of biology, and comprises CD63, HER2, GPC1 or / and EpCAM; probe sequences are shown in SEQ ID NO.1-SEQ ID NO.4; the probe is applied to the extracellular vesicle detection reagent in the separation-free plasma, single EVs imaging analysis, detection of the image of a single EV after direct dilution of plasma, dynamic immune detection, and statistics of the number of specifically combined EVs. The application applies the separation-free extracellular vesicle detection probe to the immune detection reagent, avoids the separation process of plasma EVs, does not need to use fluorescence detection, can characterize the single EVs binding kinetics, and can detect 1 target EVs in 350 background particles.

The invention relates to a composition and a kit for detecting tumor-derived tEVs and application of the composition and the kit, and belongs to the technical field of biology. In order to solve the problems of insufficient sensitivity, poor specificity and complex operation of the existing tumor-derived extracellular vesicles (tEVs) detection technology, the invention provides a composition which is composed of double aptamers for specifically recognizing PD-L1 and EpCAM proteins on the surface of the tEVs, a connecting sequence, an annular template, a branch primer, crRNA and a fluorescent probe and is combined with T4DNA ligase, Phi29 polymerase and a CRISPR / Cas12a system. The method is applied to rapid detection of tEVs. Good application prospects are shown in liquid biopsy and dynamic monitoring. Therefore, high-sensitivity and high-specificity tumor tEVs detection is realized, and a reliable tool is provided for early diagnosis of cancers.

The application discloses application of tumor-derived acellular extracellular matrix in preparation of a drug for promoting angiogenesis and tissue regeneration. The application proposes a strategy for regulating tissue regeneration based on a tumor-derived acellular extracellular matrix microenvironment, combines the high similarity between a tumor microenvironment and a regeneration microenvironment such as angiogenesis, and constructs a novel angiogenesis-promoting biomaterial, so that high-efficiency regeneration is realized in various tissue defects. In addition, the characteristics of rapid proliferation of tumor tissues break through the production capacity bottleneck of a raw material source of a traditional acellular extracellular matrix, and provide sustainable biological raw materials for large-scale production. The application successfully solves the problem that a specific tissue-derived acellular extracellular matrix is difficult to regenerate in a complex damage microenvironment.

The present invention relates to the field of pharmacogenomics and in particular to detecting the presence or absence of methylated ANKRD13B and / or FOXF2 DNA derived from a tumor in blood or blood-derived samples or in other body fluids that contain DNA released from a tumor. This detection is useful for a minimally invasive diagnosis of cancers and the invention provides methods and oligonucleotides suitable for this purpose.

To provide a method for quantifying molecular activity in cancer cells of human tumors, which predicts expression profiles of cancerous cells and non-cancerous cells respectively based on multiple sets of expression profiles.SOLUTION: A method includes the steps of: obtaining each set of multiple sets of expression profiles from tumour-derived samples including a mixture of cancerous cells and non-cancerous cells of one tumour type and determining tumour purity values for the tumour-derived samples; providing the multiple sets of expression profiles including combined expression data for multiple or all molecules expressed by cancerous cells and non-cancerous cells included in the tumour-derived samples; and deconvoluting each combined expression data by extrapolating expression profiles to a tumour purity value at least substantially equal to 1 or 0, thereby predicting the expression profiles of the cancerous cells and the non-cancerous cells respectively.SELECTED DRAWING: Figure 3

Provided herein are methods for differentiating tumor and non-tumor (e.g., clonal hematopoiesis of indeterminate potential (CHIP)) origin nucleic acid variants from one another in a test sample obtained from a test subject at least partially using a computer. Other aspects are directed to methods of treating disease in subjects. Yet other aspects include related systems and computer readable media used to differentiating tumor and non-tumor origin nucleic acid variants from one another.

As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Neuroendocrine tumors (NETs) are highly heterogeneous tumors derived from neuroendocrine cells. The synaptic vesicle 2 (SV2) protein is a novel marker of NETs and has three subtypes of SV2A, SV2B and SV2C, the SV2C structure is more stable than the other two subtypes, and the maximum cavity ring L4 is the most important binding region with toxins. The nano antibody of the extracellular soluble part L4 of the SV2 is obtained by screening through a phage display technology, the obtained nano antibody is labeled by fluorescein, chemical toxin small molecules or nuclide to prepare a probe molecule, and the result can specifically bind to neuroendocrine tumor cells. The invention provides a nano antibody of an extracellular soluble part L4 of SV2. The nano antibody can be applied to preparation of a preparation for diagnosing and treating neuroendocrine tumors.

Disclosed herein are DNA amplification methods for quantifying DNA fragments of a target DNA in a sample by size. This can be used, for example, to detect tumor-derived viral DNA in blood sample and distinguish it from larger viral DNA from non-tumor sources. In particular, disclosed herein are methods of detecting, monitoring or treating a human papilloma virus (HPV)-associated malignancy in a subject that involves detecting a presence or absence of at least one circulating tumor-derived HPV DNA in a sample from the subject. Kits for accomplishing the same are also provided.

The invention provides a preparation method of SPF (specific pathogen free) pigskin extracellular matrix (ECM) hydrogel. The preparation method comprises the following steps: S1, collecting SPF pigskin and pretreating; s2, the pretreated SPF pigskin is subjected to degreasing treatment; s3, sterilizing and disinfecting the freeze-dried powder, and then carrying out enzymolysis; s4, adjusting the pH and osmotic pressure of supernate after enzymolysis to obtain a hydrogel product. The source of the hydrogel product does not contain non-biological source materials at all, establishment of a three-dimensional cell culture environment and growth of cultured cells, especially organoids are facilitated, and meanwhile the problems of tumor sources, batch differences, high cost, potential safety hazards and the like of existing hydrogel products such as Matrigel and the like are solved. Experimental results show that the pigskin ECM hydrogel with different concentrations and from different ages can support the growth of intestinal organs, and the number of the organs cultured by the SPF pigskin ECM hydrogel with the concentration of 3 mg / mL is even more than that of Matrigel.

The application relates to the technical field of nanomaterials, in particular to an EpCAM aptamer modified nanomaterial and a preparation method and application thereof, wherein the nanomaterial takes carboxylated mesoporous silica nanoparticles as a carrier, and an EpCAM specific DNA aptamer is covalently coupled to the surface of the nanomaterial; the sequence of the EpCAM specific DNA aptamer is shown as SEQ ID No. 1. The nanomaterial can specifically capture tumor-derived exosomes (EVs) in blood, and can realize sensitive detection of EVs in the 7-day (early stage) and 21-day (late stage) stages of an HT29 colon cancer model and the 7-day stage of an A549 / H460 lung cancer model, thereby providing a minimally invasive liquid biopsy new tool for early diagnosis of colon cancer and lung cancer, and solving the inherent limitation problems of sensitivity and specificity of existing diagnosis means in cancer detection.

The present invention relates to the field of biomedicine technology, and mainly to the use of tumor-derived monocytes in the preparation of drugs for treating Alzheimer's disease. The present invention applies tumor-derived monocytes to the treatment of diseases for the first time. Experiments of the present invention have shown that tumor-derived monocytes can improve and treat Alzheimer's disease, and can also play a role in improving cognitive ability and effectively improve the pathological phenotype of Alzheimer's disease. At the same time, experiments have shown that tumor-derived monocytes only need to be injected once to maintain the therapeutic effect, and will not cause abnormal immune response and tumor occurrence. The tumor-derived monocytes proposed by the present invention have great application prospects in the treatment and prevention of AD.

Disclosed herein are compositions of antigen-presenting tumor cells (APTCs) and tumor-derived antigen-presenting vesicles (Tumor-APVs) derived from APTCs and methods of their use.

The present disclosure relates to attenuated yet immunogenically potentiated tumor-derived extracellular vesicle compositions and uses thereof. The present disclosure was completed by confirming that the extracellular vesicles secreted by tumor cells are attenuated yet immunogenically potentiated through a process of treating tumor cells with verteporfin, and the extracellular vesicles of the present disclosure can be used as a vaccine composition, etc.

This invention belongs to the field of biomedical technology and provides the application of exosome-derived TRIM59 inhibitors in regulating macrophage M2 polarization and combating oral squamous cell carcinoma. The TRIM59 inhibitor uses exosomes derived from oral squamous cell carcinoma tissue as carriers, with the surface modified with the M2 macrophage-targeting molecule M2pep, internally loaded with TRIM59 inhibitors and KRT6B inhibitors, and loaded with STING pathway agonists. This invention relies on the microenvironment targeting and membrane surface targeting modification of tumor-derived exosomes to precisely deliver TRIM59 inhibitors and KRT6B inhibitors to M2 macrophages and tumor cells. By silencing TRIM59, the resistance of M2 macrophages to the STING pathway is relieved, forming a temporal synergistic effect of first unlocking and then activating with the STING agonist, driving macrophages to M1 polarization.

The invention belongs to the technical field of biological detection, and particularly relates to a synchronous detection sensor for two membrane proteins of tumor-derived small extracellular vesicles based on CRISPR / Cas9. Comprising the following steps: (1) aptamers AptEGFR and AptPD-L1, which are targeted to EGFR (epidermal growth factor receptor) and PD-L1; the magnetic nano particles are modified with an aptamer AptEpCAM (Aptamer EpCAM); (2) a compound of sgRNA1, sgRNA2 and Cas9 protein, wherein the sgRNA1 and the sgRNA2 can be hybridized with nucleic acid sequences at the tail parts of the aptamers AptEGFR and AptPD-L1; the long-stem hairpin probe W1 and the long-stem hairpin probe W2 can be respectively identified by the sgRNA1 and the sgRNA2 and can be cut by the Cas9 protein to release ssDNA Act1 and Act2; (3) hairpin probes H1, H2, H3 and H4; cHA1 is formed by the Act1, the hairpin probe H1 and the hairpin probe H2, and CHA2 is formed by the Act2, the hairpin probe H3 and the hairpin probe H4. The sensor provided by the invention has potential clinical application value in lung cancer screening and auxiliary diagnosis.

Various embodiments of the present invention provide compositions of tumor-infiltrating lymphocytes (TILs) enriched with tumor-reactive cells. The embodiments also provide methods for producing tumor-reactive TILs enriched with tumor-reactive cells, and the use of the provided enriched tumor-reactive TILs for treating cancer in humans or other subjects. According to the embodiments, a tumor-reactive T cell enriched pharmaceutical T lymphocyte infiltration (TIL) composition comprises an oligoclonal population of tumor-infiltrating T cells, including tumor-derived CD4+ and CD8+ T cells, with up to 40 clones constituting 40% of the TCR frequency in the population. Embodiments of the present invention are particularly useful for treating tumors that are resistant or refractory to conventional chemotherapy, or that have become resistant or refractory.

The invention discloses an anti-osteosarcoma combined pharmaceutical composition and application thereof. The combined pharmaceutical composition comprises a TNF alpha inhibitor and a chemotherapeutic drug. According to the invention, the TNF alpha inhibitor and the traditional chemotherapeutic drug are combined for use for the first time to resist osteosarcoma, so that the purposes of synergistic tumor inhibition, toxicity reduction and sensitization are achieved. By intervening a neglected chemotherapy side reaction pathway of tumor-liver axis, tumor-derived extracellular vesicles are blocked to induce Kupffer cells to release TNF alpha, liver lipid droplet deposition is reduced, and expression (including Cyp1a2, Cyp2b10, Cyp3a11 and the like) of CYP metabolic enzymes is recovered, so that the metabolic capability of the liver to chemotherapy drugs is improved, and toxic and side effects are reduced. From the perspective of chemotherapy tolerance and toxic and side effect control, cardiotoxicity and myelosuppression are remarkably reduced, the overall tolerance to a chemotherapy regimen is improved, and a safer and more efficient strategy is provided.

The invention belongs to the technical field of medicines, and particularly relates to a construction method of a peripheral blood circulating tumor DNA and RNA co-construction library and a kit for detecting tumor mutation. The invention provides a peripheral blood circulating tumor DNA and RNA co-construction library and a construction method thereof. By adopting the ctDNA and ctRNA co-established library, more tumor-derived mutations can be detected, mutation types missed by the ctDNA library are found, and mutation characteristic identification of tumor cells of tumor patients is realized more accurately and sensitively.

The invention belongs to the technical field of tumor animal models, and particularly relates to a construction method and application of a brain glioma PDTX model. The invention formulates a tumor screening method suitable for constructing the brain glioma PDTX model, tumor samples with relatively high GFAP, SOX2, SLC1A3 and OLIG2 gene transcription levels are screened as ideal tumor sources by performing transcriptome sequencing on tumor tissues, and the model is constructed by the novel brain glioma PDTX model construction method provided by the invention. According to the method, the screened brain glioma tissue is transplanted into the immunodeficient mouse, so that the original microenvironment characteristics of the tumor can be effectively reserved, and the success rate of constructing the brain glioma PDTX model is obviously improved.

The present invention discloses a non-invasive early screening method and system for cancer based on the length distribution characteristics of cfDNA fragments. This method uses a relatively low-depth whole-genome sequencing method to statistically analyze the differences in the fragment length distribution characteristics of tumor-derived cfDNA and healthy individual-derived cfDNA, establish an early screening model for cancer, and achieve non-invasive early screening for cancer. The scheme of the present invention focuses on the characteristic of blood cfDNA fragment size to distinguish ctDNA from non-tumor-derived cfDNA. It does not rely on the mutation detection of oncogenes or tumor suppressor genes, and eliminates the interference caused by clonal hematopoietic mutations. Secondly, the data of the embodiments of the present invention show that the size characteristics of blood cfDNA fragments can be used to distinguish between healthy people and early-stage tumor patients. Finally, due to the use of low-depth whole-genome sequencing technology, the detection costs involved in the scheme of the present invention are greatly reduced, which is conducive to future applications in the field of early screening of malignant tumors.

To provide methods for classifying genetic mutations detected in cell-free nucleic acids as tumor or non-tumor origin.SOLUTION: Methods for differentiating tumor and non-tumor origin nucleic acid variants in cell-free nucleic acid (cfNA) samples include generating a tumor variant dataset comprising a population of reference tumor-related genetic variants. The tumor variant dataset comprises frequency of observance data among reference samples that comprises reference bodily fluid (e.g., plasma) samples and reference non-bodily fluid (e.g., non-plasma) samples for tumor-related genetic variants in the population of reference tumor-related genetic variants. The methods further include determining ratios of the frequency of observance data between the reference samples for tumor-related genetic variants in the population of reference tumor-related genetic variants to produce a relative prevalence dataset.SELECTED DRAWING: Figure 2

Methods for levels of evidence-based categorization of tumor profiling results are described. The methods may comprise, for example, receiving tumor profiling results for a tumor derived from a subject; determining if a genomic alteration identified in the tumor profiling results is associated with an approved companion diagnostic finding; determining if the genomic alteration identified in the tumor profiling results is listed as a predictive marker of drug sensitivity or drug resistance for a given tumor type in at least one applicable guideline document; and reporting the genomic alteration as: (i) a Level 1 genomic alteration if the genomic alteration is associated with an approved companion diagnostic finding, or (ii) a Level 2 genomic alteration if the genomic alteration is listed as a predictive marker, or (iii) a Level 3 genomic alteration if the genomic alteration is not listed as a predictive marker.

The invention discloses a pharmaceutical composition containing a tumor-derived acellular extracellular matrix and an application of the pharmaceutical composition. The invention provides a strategy for regulating and controlling tissue regeneration based on a tumor-derived acellular extracellular matrix microenvironment, a novel angiogenesis promoting biological material is constructed by combining the high similarity of a tumor microenvironment and a regeneration microenvironment such as angiogenesis, and high-efficiency regeneration is realized in various tissue defects. In addition, due to the characteristic of rapid proliferation of the tumor tissue, the productivity bottleneck of a traditional acellular extracellular matrix raw material source is broken through, and sustainable biological raw materials are provided for large-scale production. The method successfully solves the problem that a specific tissue-derived acellular extracellular matrix is difficult to regenerate in a complex damaged microenvironment.