1411 results about "Solid tumor" patented technology

A pharmaceutical composition comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and a KRASG12C (Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine) inhibitor. The pharmaceutical composition can be used for treating various cancers, comprising solid tumors. The combined product can be used for treating any number of diseases associated with PRMT5 and / or KRASG12C.

The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, the disclosure provides compounds of Formula (I):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

The invention discloses a medical developing marker and a manufacturing method thereof, and relates to the field of medical instruments, the medical developing marker comprises a closed tube, the outer wall of the closed tube is provided with a bionic barb structure, the bionic barb structure is distributed in a flexible zigzag convex manner, and the bionic barb structure and the closed tube are integrally formed through an injection molding process; a closed cavity is arranged in the closed tube, four developing strips are symmetrically arranged in the tube wall of the closed cavity, the tube wall of the region where the developing strips are located is etched to form a weak band, and a developing material layer and a sustained-release medicine layer are sequentially deposited at the weak band. The developing material layer and the sustained-release drug and / or marked nano-particle layer are alternately deposited to form a functional composite layer, and the functional composite layer can directionally rupture to release the therapeutic drug under the action of implantation pressure. The marker integrates the functions of precise development, tissue anchoring and drug sustained release, is adaptive to multi-mode imaging such as ultrasonic imaging, X-ray imaging, CT imaging, MRI imaging and PET-CT imaging, and has remarkable clinical value in precise positioning treatment of solid tumors such as breast cancer and liver cancer.

The invention belongs to the technical field of medical pathological images, and particularly relates to a multi-instance multi-task learning pan cancer biomarker prediction method and system, and the method comprises the steps: obtaining a full-view digital pathological image and pan cancer biomarker expression data of a solid tumor patient; performing preprocessing and feature extraction based on the full-view digital pathological image to obtain a pathological feature data set; based on the pathological feature data set, inputting the pathological feature data set into a twin multi-example full convolutional network model for training to obtain pathological low-dimensional features, and calculating an attention score corresponding to each pathological feature in combination with a linear attention mechanism; and in combination with each pathologic low-dimensional feature and the corresponding attention score, calculating to obtain a pathologic depth feature, and inputting the pathologic depth feature into a multi-task classification prediction model for classification prediction to obtain a prediction result of each biomarker in the pan cancer.

The invention discloses a lysosome targeted chimera based on Sortilin and application thereof. The lysosome targeted chimera comprises a ligand molecule of a lysosome targeted receptor and a ligand molecule of a targeted protein to be degraded, wherein the ligand molecule and the ligand molecule are connected through a linker; the lysosome targeting receptor is Sortilin, and the ligand molecule of the lysosome targeting receptor is a polypeptide targeting the Sortilin; the protein to be degraded is membrane protein or extracellular protein. Furthermore, the polypeptide of the targeted Sortilin is connected with an enzyme response sequence and an integrin receptor targeting sequence. According to the invention, the Sortilin-combined ligand neurotensin is functionally coupled with the neutralizing antibody or polypeptide of overexpression protein in targeted tumor or inflammatory diseases, and the Sortilin-combined ligand neurotensin has obvious treatment gain in malignant solid tumor and psoriasis models. The discovery promotes the transformation potential of the lysosome participating in the biological agent, and provides a dual strategy for realizing accurate degradation through receptor recruitment and microenvironment induction.

Provided herein are novel cyclic peptides, their synthetic process, compositions, properties including stability and pharmacokinetic profiles, and applications for treating solid tumor cancers.

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 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 relates to the field of tumor cell therapy, in particular to application of T lymphocyte chimeric with a B7-H3 receptor to treatment of head and neck tumors, and provides an anti-B7-H3 scFv, the scFv comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an HCDR region and an HFR region, and the light chain variable region comprises an LCDR region and an LFR region; compared with a wild type scFv sequence, the scFv sequence has the advantage that a plurality of amino acids with positive charges in the HFR region and / or the LFR region are mutated into amino acids without charges. According to the invention, positive charge plaques on the CAR surface of an scFv sequence of a B7-H3 human-derived monoclonal antibody MGA271 are changed in a charged amino acid mutation manner, so that a B7-H3. CAR-T cell is optimized, and it is proved that the B7-H3. CAR-T cell optimized by PCP can effectively kill B7-H3 positive tumor cells in vivo and in vitro; and a new method and thought are provided for clinical targeted treatment of B7-H3 positive solid tumors.

The invention belongs to the field of biomedicine, and particularly relates to polypeptide for targeted blocking of combination of TRIM25 and BRD7 protein and application of the polypeptide. According to the present invention, based on the minimum binding region PRYSPRY structural domain (439 aa-630 aa) of the TRIM25 and the BRD7 protein, the blocking peptide TB16 capable of specifically blocking the mutual binding of the TRIM25 and the BRD7 protein is screened, such that the ubiquitination degradation of the BRD7 is inhibited, and the stability of the BRD7 tumor inhibition protein is improved. The polypeptide drug TB16 can effectively inhibit breast cancer, nasopharynx cancer, ovarian cancer, lung cancer and liver cancer cell proliferation and breast cancer in-vivo tumor growth, has good anti-solid tumor activity, and is expected to become a new anti-tumor targeting drug.

An antibody capable of binding to LILRB4 and a bispecific antibody capable of binding to LILRB4 and CD3 are provided. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. Also provided are methods of treating solid tumors, multiple myeloma or leukemia, such as acute myelogenous leukemia (AML), using the anti-LILRB4xCD3 double antibodies of the present invention.

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

The present invention relates to the field of optical imaging. More specifically, the present invention relates to a class of monoalkylated cyanine dyes having red to near-infrared (650-900 nm) emission, characterized by pH responsiveness, and to conjugates thereof with biological ligands. The present invention also relates to the use of these compounds as optical diagnostic agents in the imaging or therapy of solid tumors, to methods for their preparation and to compositions containing them. The monoalkylated cyanine dyes have the general formula (I), in which R1 and R3 are independently selected from the group consisting of hydrogen, -SO3H, -COOH and -CONH-Y; and R2 and R4 are hydrogen, or R1 together with R2 and R3 together with R4 both form two aryl rings optionally substituted by 1 to 4 -SO3H groups together with the atoms to which they are bonded; R5 is an alkyl group optionally substituted by a group selected from -SO3H, -COOH and -CONH2. #imgabs0#

The invention provides a CLDN6 single domain antibody and a humanization method thereof. The CLDN6 single-domain antibody provided by the invention has targeted specificity to CLDN6, only recognizes the CLDN6 and does not recognize CLDN3, CLDN4 and CLDN9 of the same family, or the recognition modes are obviously different. The CLDN6 single-domain antibody 1H07 with targeting specificity provided by the invention can be used for constructing a chimeric antigen receptor (CAR) and a bivalent antibody (bispecific antibody). The CAR constructed based on the antibody sequence can be transduced into a T cell to create a CAR-T cell specifically targeting CLDN6, and the CAR-T cell can be used for treating solid tumors such as ovarian 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 a preparation method and application of a CD70 specific nano antibody molecular imaging probe. The probe comprises a tumor targeting group, radionuclide and a bifunctional chelating agent, the tumor targeting group is a CD70 specific nano antibody; the CD70 specific nano antibody is R8B4, and the amino acid sequence of the R8B4 is as shown in SEQ ID No. 1. The probe provided by the invention can realize noninvasive diagnosis of solid tumors such as renal clear cell carcinoma and malignant tumors of a blood system; reabsorption of the compound in the kidney is effectively inhibited through charge adjustment, kidney uptake is remarkably reduced, non-specific signals are reduced, the signal-to-noise ratio during targeted imaging or treatment is increased, and the imaging quality and treatment safety are improved. The probe not only has a wide application prospect in tumor diagnosis, but also provides a new technical support for targeted therapy and individualized precision medical treatment, and has important scientific research and clinical application values.

The invention discloses a construction method and application of a gastric cancer treatment effect evaluation model of CAR-T cells, and the constructed gastric cancer treatment effect evaluation model of the CAR-T cells comprises a CAR-T cell and gastric cancer organ co-culture killer dynamic detection system and a CAR-T cell, intestine organ and lung organ co-culture safety evaluation system. Based on a CAR-T cell and gastric cancer organoid co-culture lethality dynamic detection system, the process that CAR-T cells act on gastric cancer organoid can be dynamically observed through a living cell imaging method, then the action mechanism of the CAR-T cells for treating solid tumors is studied, and meanwhile, based on a CAR-T cell, intestine organoid and lung organoid co-culture safety evaluation system, the CAR-T cells and the gastric cancer organoid co-culture lethality dynamic detection system can be used for evaluating the CAR-T cells and the gastric cancer organoid co-culture lethality. Compared with the prior art, the preclinical model has the advantages that the effect of the CAR-T cells on gastric cancer para-tissues and other tissue-derived organs can be detected, and safety evaluation is carried out, so that the preclinical model for more comprehensively detecting the gastric cancer treatment effect of the CAR-T cells is obtained, and the research on CAR-T cell targets is facilitated.

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 discloses an engineered NK cell and a preparation method thereof. The antitumor activity of the NK cell is enhanced through synergistic modification of a fusion polypeptide and an anti-TIGIT monoclonal antibody. The amino acid sequence of the fusion polypeptide is shown as SEQ ID NO.1. The fusion polypeptide can specifically target tumor cells and activate the proliferation and killing functions of NK cells. And the anti-TIGIT monoclonal antibody further relieves the immunosuppression by blocking a TIGIT-CD155 signal channel. In-vitro experiments show that the killing rate of the combined modified NK cell on various solid tumors is obviously higher than that of the traditional CAR-NK cell. A PDX model shows that the engineered NK cells significantly inhibit tumor growth and enhance NK cell infiltration in a tumor microenvironment. The invention provides a new strategy with high efficiency and low toxicity for immunotherapy of solid tumors.

A pharmaceutical composition comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and a methionine adenosyltransferase IIα (MAT2A) inhibitor. The pharmaceutical composition can be used for treating various cancers, comprising solid tumors. The combined product can be used for treating any number of diseases associated with PRMT5 and / or MAT2A.

The present disclosure provides engineered immune cells modified to overexpress tumor sensing enhancer proteins, thereby providing the engineered immune cells with an enhanced ability to migrate to and / or infiltrate tumors. In some examples, the tumor sensing enhancer proteins are tumor sensing receptors that specifically bind to non-chemokine receptors. The disclosure also provides methods including the provided engineered immune cells.

Provided herein are SHP2 inhibitors for use in the reduction of solid tumors in a method of treating cancer.

The present invention pertains to the technical field of drug application and particularly relates to clinical use of a KRAS G12D inhibitor. The inhibitor can be clinically used to effectively treat patients with advanced solid tumors carrying the KRAS G12D mutation and can produce beneficial effects.

The present disclosure relates to methods for treating a tumor or a cancer, optionally a solid tumor, in an individual, the method comprising administering to the individual a menin inhibitor and an immuno-oncology agent.

Disclosed is a pharmaceutical composition, comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and an epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor. The pharmaceutical composition can be used to treat various cancers, including solid tumors. The combination product can be used to treat any number of diseases associated with PRMT5 and / or EGFR.

Provided herein are novel cyclic peptides, their synthetic process, compositions, properties including stability and pharmacokinetic profiles, and applications for treating solid tumor cancers.

Provided herein are novel anti-effector moiety antibodies or antigen binding domains thereof, and CARs comprising such effector moiety antigen binding domains with or without one or more enhancer elements, as well as host cells expressing the receptors and nucleic acid molecules encoding the receptors, and methods of using the same in patient-specific immunotherapy useful for the treatment of solid tumor cancers and other diseases and disorders.

The invention belongs to the technical field of nano-medicines and targeted therapy, and particularly relates to a targeted nano-system nano-drug delivery system based on mesoporous polydopamine as well as a preparation method and application thereof, in particular to an N2E4-MPDA-Gem nano-system based on mesoporous polydopamine (MPDA). A targeting nano system based on mesoporous polydopamine comprises mesoporous polydopamine nano particles loaded with pancreatic cancer chemotherapy drugs, targeting molecules N2E4 are combined with the surfaces of the mesoporous polydopamine nano particles, and phenylboronic acid coatings used for controlling drug release are arranged on the surfaces of the mesoporous polydopamine nano particles. The system adopts a modular design, can be compatible with various chemotherapeutic drugs such as oxaliplatin, irinotecan and the like, and can be flexibly coupled with different targeting antibodies such as EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor) and the like. A standard preparation process and good stability provide reliable guarantee for clinical transformation, and the compound shows an excellent treatment effect in a solid tumor model represented by pancreatic cancer.

The invention relates to a noninvasive solid tumor internal hypoxia condition detection method, which comprises: chemically modifying a near-infrared two-region fluorophore, an oxygen sensitive group and a tumor targeting group to construct a composite probe, collecting fluorescence and photoacoustic signals of a tumor region after intravenous injection, carrying out de-noising analysis, and combining with multiple parameters to solve hypoxia concentration change, a four-dimensional space-time distribution map is constructed by fusing vascular topological data, and individualized calibration is realized through microfluidic simulation and Bayesian optimization. Compared with a traditional invasive detection and single-mode imaging technology, the advantages of bimodal signals are integrated in a breakthrough mode, non-invasive, real-time and high-resolution dynamic hypoxia monitoring is achieved, acute and chronic hypoxia areas are accurately distinguished, tumor blood vessel heterogeneity interference is reduced through personalized parameter calibration, and the accuracy of hypoxia monitoring is improved. High-precision spatio-temporal data support based on hypoxia microenvironment monitoring is provided for solid tumor radiotherapy target planning, chemotherapy drug delivery optimization, chemotherapy drug resistance and curative effect prediction and evaluation and tumor metastasis progress risk analysis.

Provided herein is a method of treating solid tumor. In particular, provided is a method of treating solid tumor, such as advanced and / or metastatic solid tumor, by using a bispecific antibody.