714 results about "Solid tumor" patented technology

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

The invention provides an intraoperative path optimization method and system based on solid tumor preoperative image analysis, and the method comprises the steps: constructing a three-dimensional model of a tumor and peripheral blood vessels and nerves according to a preoperative image, and carrying out the dissection risk marking of the three-dimensional model through a deep learning model, generating an anatomical risk image with risk gradient value distribution; taking the minimum intraoperative bleeding amount and the highest tumor excision rate as a reward function, combining the three-dimensional model, an anatomical risk image and historical similar case data, and simulating multiple operation paths based on an adversarial reinforcement learning algorithm to obtain an optimal operation path; the method comprises the following steps: acquiring the pose, ultrasonic image and fluorescence image of a surgical instrument in real time during surgery, matching the preoperative image with the intraoperative image based on a biomechanical model driven non-rigid registration algorithm, predicting organ displacement, and correcting an optimal surgical path, thereby avoiding accidental injury of key tissues, ensuring that an infiltration area is brought into the surgical path in time, and improving the surgical efficiency. Residues are reduced, and static planning failure is avoided.

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 preparation of a GSH responsive photo-thermal chemical synergetic liquid metal nanocomposite and application of the GSH responsive photo-thermal chemical synergetic liquid metal nanocomposite in tumor treatment, and relates to the field of nano biomedical materials. According to the composite material, gallium-tin alloy (GaSn) is used as an inner core, a reduced graphene oxide (RGO) middle layer and a manganese dioxide (MnO2) outer shell are sequentially coated, a three-layer core-shell structure is formed, and the average particle size is controlled to be about 60 nm. The liquid metal composite nanomaterial has excellent photothermal conversion performance and oxidation resistance. The compound not only can be used for treating tumors and cancers, quickly killing cancer cells and effectively inhibiting tumor growth, but also can quickly deplete GSH, break dynamic balance of redox and improve ROS level in cells. Experiments show that the material shows a remarkable inhibition effect on tumor cells, has good biocompatibility and regulation and control release characteristics, and provides a new strategy for precise synergistic treatment of solid tumors.

The present disclosure describes systems and methods for cell therapy. Cells (e.g., stem cells, immune cells, cardiomyocytes, etc.) may be engineered to exhibit extended half-lives as compared to control cells (e.g., non-engineered cells). The cells may be engineered to exhibit increased proliferative activity as compared to control cells. In some embodiments, immune cells may be engineered to efficiently and specifically target diseased cells (e.g., cancer cells) while control cells are insufficient or unable to target the diseased cells. In some embodiments, stem cells or differentiated cells, such as myocardial cells, may be administered to a target tissue for enhanced tissue engineering or regenerative medicine. The engineered cells disclosed herein can be engineered ex vivo, in vitro, and in some embodiments in vivo. Engineered cells prepared ex vivo or in vitro may be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumor). The engineered cell may be autologous to the subject. Alternatively, the engineered cell may also be allogeneic to the subject.

The present application relates to the field of immunology, and particularly relates to a novel IL-15 fusion protein and application thereof. The present application provides an IL-15 transmembrane fusion protein, which is applied to NK cells or CAR-NK cells, can significantly enhance the tumor killing function of NK cells and CAR-NK cells, and can effectively promote the proliferation of NK cells and CAR-NK cells. It provides an important basis for developing NK cell products armored by the IL-15 transmembrane fusion protein, which are independent of any tumor target, thereby reducing the cycle and cost of CAR-NK development. Meanwhile, the present application respectively carries out function research in blood tumors expressing CD19 and solid tumors expressing CD276, and the results indicate the broad-spectrum application prospect of the structure in tumors.

Systems and methods for characterizing a mutation include obtaining reference sequence reads mapping to a genomic location of the mutation from a first sequencing reaction using a reference sample of a subject, and obtaining tumor sequence reads mapping to the genomic location of the mutation from a second sequencing reaction using a solid tumor sample of the subject. A reference base fraction of the mutation is determined using the reference sequence reads. A germline expectation of the mutation is determined using a tumor purity of the solid tumor sample, the major and the minor copy number at the genomic location of the mutation derived from tumor sequence reads. The reference base fraction and the germline expectation of the mutation are inputted into a model thereby obtaining, as output from the model, a determination of whether the mutation is a clonal hematopoiesis of indeterminate potential mutation or a germline mutation.

The presently disclosed subject matter provides methods and kits for treating solid tumors in a subject by using a combination of anti-CTLA-4 and / or anti-PD-1 antibodies with at least one member of the group consisting of a bacterium, bacterial product, and an immunoregulatory entity. In particular embodiments, the bacteria are toxin-depleted, anaerobic bacteria, such as Clostridium novyi-NT.

The invention provides an application of pentafluridol in preparation of a medicine for inhibiting formation of tumor-associated fibroblasts. Specifically, the invention finds that the pentafluridol can influence the formation process of the tumor microenvironment of the targeted tumor-related fibroblast cells, and the development of solid tumors is effectively inhibited from the source, so that the increase of the tumor volume is inhibited.

The invention discloses a gamma-glutamyl transpeptidase catalytic hydrolysis induced charge upset polymer, which contains a gamma-glutamyl transpeptidase response element part and a fluorescent probe corresponding fragment part, the invention also discloses a preparation method of the polymer for turning charge by catalytic hydrolysis of gamma-glutamyltranspeptidase and an application method of the polymer in the field of tumor imaging. According to the present invention, the gamma-glutamyltranspeptidase catalytic hydrolysis electric charge overturning polymer is adopted as the response type tumor imaging probe, such that the electric charge can be converted from the negative or neutral state to the positive state so as to achieve the rapid uptake of the positively charged polymer by the tumor cells so as to achieve the rapid spraying imaging, and the probe response after the uptake is adopted so as to achieve the rapid spraying imaging; the imaging effect of the probe on the tumor is greatly improved, and the probe has important significance in solid tumor imaging for assisting a doctor in surgical resection.

The invention relates to a capture probe group, a kit and a sequencing library for detecting polymorphism of related genes of solid tumor chemotherapy drugs and a construction method of the sequencing library, and belongs to the technical field of high-throughput detection. The capture probe group for detecting the polymorphism of the related genes of the solid tumor chemotherapy drugs comprises nucleotide sequences as shown in SEQ ID NO.1 to SEQ ID NO.12; the related genes of the solid tumor chemotherapeutic drugs comprise MTHFR (Methylene Tetrahydrofolate Reductase), TP53, TPMT (Trimethylparaben Methyl Methyl Thiazolyl Tetrazolium), XRCC1 (XRCC1), DPYD ( According to the capture probe group, genotypes of genes related to solid tumor chemotherapy can be rapidly obtained through one-time detection, a sequencing library is constructed on the basis of the genotypes, and related information such as medication prompt, drug curative effect, toxicity and metabolic capacity corresponding to a clinical sample is obtained according to the genotypes of the sequencing library; the kit is simple and convenient to operate, consumes less time and is extremely easy to realize automatic detection.

The invention relates to the technical field of tumor molecular imaging, nuclear medicine diagnosis and targeted therapy, and discloses a Trop2-targeted polypeptide, a Trop2-targeted molecular probe and application of the Trop2-targeted polypeptide and the Trop2-targeted molecular probe. The polypeptide can be coupled with different imaging elements to construct molecular probes or radiopharmaceuticals for tumor targeted imaging, so that noninvasive visual detection on the Trop2 expression level in tumor tissues is realized. The probe can specifically recognize Trop2 positive solid tumors, and a new technical means is provided for noninvasive diagnosis and dynamic monitoring of various Trop2 high-expression tumors such as pancreatic cancer, lung cancer, breast cancer and thyroid cancer. The probe disclosed by the invention has the advantages of simple preparation process, low cost, high specificity and stability, short imaging period, low radiation dosage, easiness in clinical transformation and the like, and has a wide application prospect in precise diagnosis and individualized treatment of tumors.

The invention provides a three-specificity immune cell adapter-cytokine fusion protein for malignant tumor immunotherapy as well as a preparation method and application of the three-specificity immune cell adapter-cytokine fusion protein. The fusion protein comprises a first binding domain, a second binding domain and a cytokine structural domain which are covalently linked to form a single polypeptide chain or polypeptide compound. The first binding domain is specifically bound with a tumor associated antigen, and the target spot of the first binding domain comprises but is not limited to KK-LC-1, MSLN, HER2, Claudin18.2, Claudin6 and PSMA; the second binding domain is specifically bound with a CD3 protein complex on the surface of the T cell; the cytokine domain is IL2, IL15, IL12, IL21 or a functional variant thereof. The invention also relates to a nucleic acid molecule for coding the fusion protein, an expression vector and application thereof. The fusion protein can be used for immunotherapy of malignant tumors such as colon cancer, gastric cancer, breast cancer, liver cancer, lung cancer and cervical cancer, and has a good application prospect. The invention effectively solves the problems of insufficient T cell activation and limited killing in solid tumor immunotherapy in the prior art.

The invention relates to a bispecific antibody-cytokine fusion protein as well as a preparation method and application thereof. The fusion protein comprises a TAA binding unit, a T cell binding unit and a cytokine unit, the TAA binding unit comprises an anti-HER2 structural domain, the T cell binding unit comprises an anti-CD3 structural domain, and the cell factor unit comprises IL-2; the anti-CD3 structural domain and the IL-2 structural domain can act on T cells at the same time, further amplification of the T cells is promoted while the T cells are activated to generate cytotoxic killing, the anti-CD3 structural domain and the IL-2 structural domain can be directionally migrated to the periphery of HER2 positive tumor cells through the anti-HER2 structural domain, the efficiency of promoting proliferation and differentiation of tumor infiltrating T cells is improved, and the T cells can be effectively degraded. The effect of killing solid tumor cells by immune cells is greatly improved, the non-specific killing effect of the fusion protein on normal cells and the accompanying release of cytokines in peripheral blood can be reduced to the minimum, and the toxic and side effects of the fusion protein in clinical treatment are reduced.

The invention discloses an HER2-CAR lentivirus and application thereof, and belongs to the technical field of lentiviruses. The invention provides the CAR with a brand new structure, the expression level, the stability and the targeting property of the CAR protein in immune cells such as T cells and NK cells can be remarkably improved, the survival time of engineered immune cells in vivo can be prolonged, the lasting anti-tumor capacity of the engineered immune cells can be prolonged, and the tumor cell removing capacity can be improved; the lentiviral vector provided by the invention is high in infection efficiency and wide in host range, provides a reliable platform for large-scale preparation of clinical-grade CAR-T / CAR-NK cell products, and has huge development potential and application value in the field of immunotherapy of HER2 positive solid tumors.

The present disclosure relates to methods of treating solid tumors by administering a therapeutically effective amount of a mitogen-activated protein kinase (MAPK) inhibitor having the structure of Compound (I): (Compound I), or a pharmaceutically acceptable salt thereof.

The application discloses an albumin nano-drug based on HSP90 inhibitor and a preparation method and application thereof, and belongs to the technical field of medicines.The short peptide A6 is modified to human blood albumin through a connecting chain, and the human blood albumin modified by the A6 is self-assembled with geldanamycin derivative G2111 in the presence of an organic solvent, so that the G2111 is combined to the hydrophobic region of the human blood albumin through a non-covalent bond, effective loading of the G2111 is realized, the solubility of the geldanamycin derivative is improved, the drug is targetedly released into cancer cells with high expression of CD44, the targeted accumulation of the drug in tumor tissues is enhanced, damage to other normal tissues and cells caused by off-target effects of the drug is avoided, the albumin nano-drug can be simultaneously used for chemotherapy of leukemia and solid tumors, and has important practical significance.

Provided are a series of 5,6-dihydrothieno[3,4-h]quinazoline compounds as represented by formula (P) and pharmaceutically acceptable salts thereof, and the use of the compounds or pharmaceutically acceptable salts thereof in the preparation of solid tumor drugs, such as solid tumor drugs associated with selective PLK1 inhibitors.

The invention discloses an application of COX4I2 in preparation of a non-small cell lung cancer medicine. Specifically, the invention also discloses an application of COX4I2 in preparation of a mitochondrial iron overload preparation and an application of a COX4I2 gene inhibitor in preparation of a preparation for promoting malignant progression of tumors. According to the invention, a COX4I2-VDAC1 interaction inhibitor is screened, a COX4I2 degradation agent or cluster-competitive peptide is developed, a brand new combined chemotherapy regimen is provided for solid tumors such as NSCLC and the like, and the polypeptide has the potential of expanding to cluster metabolic disorder diseases such as neurodegenerative diseases and diabetes mellitus.

Described herein are LAG3 specific single domain antibodies and binding molecules comprising such single domain antibodies, as well as nucleic acids encoding the same. Also provided are nucleic acids (e.g., mRNA) encoding such single domain antibodies and binding molecules and delivery vehicles (e.g., lipid nanoparticles) formulated with said nucleic acids. The disclosure also features methods of using such antibodies, binding molecules, nucleic acids, and delivery vehicles formulated with said nucleic acids to treat various diseases such as inflammatory diseases, T cell driven autoimmune diseases, and cancer (e.g., solid tumors or hematological malignancies).

The application belongs to the technical field of biological medicine, and discloses an in-situ vaccine type mRNA-tLNP preparation for solid tumor treatment and preparation and application thereof. The preparation is designed by double targets, so that CAR-T kills more tumor cells to overcome tumor heterogeneity, changes the tumor immune microenvironment through autocrine fusion proteins (anti-PD-1 scFv and TGFbetaRII, IL-15 and Flt3L, CD40L), promotes T cell proliferation, and recruits and activates dendritic cells, cross-presents new antigens in the tumor local part, and produces in-situ vaccination effects; circular RNA encoding the above proteins is prepared, and the circular RNA is wrapped by lipid nanoparticles modified by CD3 antibodies, so as to be directly delivered to the body, and a significant solid tumor treatment effect is produced.

Disclosed herein are compounds that target carbonic anhydrase 9 (CA IX) (such as compounds of structural formula (I) or (II) wherein values for variables are as described herein) and methods for the prevention and / or treatment of certain cancers, including solid tumors, using such compounds. Also disclosed herein are pharmaceutically acceptable salts of such compounds and pharmaceutical compositions comprising such compounds or salts for use in such methods of preventing or treating cancers.

This invention relates to the application of mitochondrial extracts in reversing drug resistance in solid tumors. By combining mitochondrial extracts with chemotherapeutic drugs, the resistance of chemotherapeutic-resistant solid tumors to these drugs can be reversed. Compared to using mitochondrial extracts and chemotherapeutic drugs alone, this method effectively enhances drug efficacy, thereby overcoming chemotherapeutic resistance in solid tumors. This invention, through intervention with mitochondrial extracts in different chemotherapeutic-resistant solid tumor cell lines, has verified that the combined use of mitochondrial transplantation and chemotherapeutic drugs can reverse chemotherapeutic resistance, thereby improving the efficacy of chemotherapy and opening up the possibility of continued treatment for patients with advanced solid tumors who are resistant to chemotherapeutic drugs.

Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.

1. The name of the design product: radio frequency ablation instrument. 2. The use of the design product: for the treatment of solid tumors, cardiovascular diseases. 3. The design points of the design product: in shape. 4. The picture or photo that best indicates the design points: perspective view.

The invention belongs to the technical field of biological medicines, and discloses an engineered bacterium for in-situ expression of a microtubule inhibition protein in a tumor and application of the engineered bacterium. The engineering bacteria are formed by constructing microtubule inhibition protein genes to an expression vector and finally transferring the expression vector into bacteria. The engineering bacterium can be colonized in a tumor microenvironment in a targeted manner, expresses microtubule inhibition protein, effectively inhibits tumor cells and remarkably inhibits solid tumor growth, and is excellent in safety.

The present disclosure relates to novel compounds that act as modulators of cereblon (CRBN). The compounds promote CRBN-mediated ubiquitination and proteasomal degradation of oncogenic proteins such as GSPT1 and MYC, thereby suppressing abnormal cell growth. Pharmaceutical compositions containing the compounds and methods of using the compositions for the treatment of cancers, particularly solid tumors, are also provided.

The present invention relates to engineered immune cells expressing a chimeric antigen receptor (anti-mesothelin CAR) specific for mesothelin (MLSN) and their use in the treatment of solid tumors, particularly suitable for allogeneic cell immunotherapy.

The invention discloses an autologous NK cell in-vitro culture method for improving purity and amplification multiple, and belongs to the technical field of biology. In order to overcome the defect that in-vitro large-scale amplification and activation of autologous NK cells of unhealthy people (solid tumor patients) are difficult, the autologous NK cells are obtained from peripheral blood of the patients, autologous CD3 + cells are used as trophoblast layers, the autologous NK cells of the patients are efficiently amplified in vitro, the cell purity reaches 99% or above, biosafety risks do not exist, and the autologous NK cells of the patients can be efficiently amplified in vitro. Moreover, an efficient anti-tumor effect is also shown in vivo, the bottleneck of in-vitro amplification of autologous NK cells of a patient is overcome, and a new direction is provided for cellular immunotherapy of the patient.