1118 results about "Solid tumor" patented technology

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 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.

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.

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.

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 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 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 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.

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 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.

The application belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting cross binding of human and cynomolgus monkey CD46 and application thereof. The application utilizes alpaca to generate nanoscale antibodies, the molecular weight of which is about 15 kDa, and the nanoscale antibodies can more efficiently penetrate solid tumor tissues or cross blood-brain barrier, and the binding efficiency of the antibodies and target points is as high as possible. The 11 single-domain antibodies prepared by the application have specificity of anti-human and anti-cynomolgus monkey CD46, and in the binding detection with CD46 target proteins and CD46 overexpression cells, the binding efficiency is significantly better than that of Anti-CD46 humanization antibody, and the single-domain antibodies can be used for tumor treatment. Meanwhile, the single-domain antibodies have cross binding ability of cross species, and can be directly used for preclinical pharmacodynamics and safety evaluation, without the need of developing species-specific alternative antibodies, so that the application achieves 'one target and double effect'.

Provided herein are methods of using a heteroaromatic macrocyclic ether compound (e.g., Compound 1), or a stereoisomer, or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, for treating, preventing or managing solid tumor.

The present invention provides a phantom assembly for placement of implant structures (e.g., solid tumor and normal organ surrogates) and / or optional imaging fluids (e.g., liquid or gel) for diagnosis and treatment planning. The present invention provides a capsule receiving cavity inserts allowing for the placement of implant structures, radiation detectors / measurement devices, imaging fluids, and the like within the capsule for image quality evaluation, target localization, treatment planning, and dosimetry measurements. The present invention may incorporate motion components to enable motion-resolved experimentation in imaging and radiation therapies.

The invention provides novel fusion proteins of Interleukin 15 and prodrugs, and compositions and methods of preparation thereof, useful in treating various diseases and disorders (e.g., hyperplasia, solid tumor or hematopoietic malignancy).

The invention relates to the field of biological medicine, and discloses application of a GADD34 inhibitor in preparation of a medicine for enhancing CAR-T cell tumor treatment. The invention provides an innovative strategy for inhibiting CAR-T cell depletion through targeted regulation and control of an endoplasmic reticulum stress pathway to solve the problems that in an existing CAR-T therapy, the anti-tumor activity is reduced, and the solid tumor treatment effect is insufficient due to T cell depletion. Researches find that an IRE1-XBP1 pathway is used as a core signal axis of endoplasmic reticulum stress, and excessive activation of the IRE1-XBP1 pathway can drive CAR-T cell depletion related phenotypes (such as PD-1 / LAG-3 up regulation and cytokine secretion reduction). Screening experiments show that inhibiting the upstream regulatory factor GADD34 of the IRE1 not only can effectively reduce the IRE1-XBP1 signal intensity, but also can cooperatively relieve the endoplasmic reticulum stress pressure by regulating protein translation recovery, so that the CAR-T cell steady state is more comprehensively maintained. Therefore, the GADD34 inhibitor can provide a new way for enhancing CAR-T cell tumor treatment.

The present invention relates to antibodies or antigen binding fragments thereof that specifically bind to CXCR4. The invention also relates to said antibodies for use in therapy, in the treatment of cancer, and in the treatment of solid tumors. The invention also relates to pharmaceutical compositions comprising said antibodies, nucleic acids encoding said antibodies, vectors comprising said nucleic acids, and host cells comprising said nucleic acids or vectors.

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 provides a recombinant oncolytic virus for treating solid tumors with rare and rare gene mutations, which is an OAV treatment platform subjected to triple virus structural protein gene modification and triple adenovirus serotype chimerism, and is named as NeoViron. NeoViron can directly deliver tumor neoantigens to a plurality of solid tumors, especially tumors with rare mutations, and a new general strategy is provided for treating a plurality of intractable tumors.

Provided are a bispecific antibody combination and a use thereof. The bispecific antibody combination comprises a bispecific antibody I and a bispecific antibody II. The bispecific antibody I comprises a CD3-targeting domain and a tumor-associated antigen-targeting domain, and the bispecific antibody II comprises a 4-1BB-targeting domain and a tumor-associated antigen-targeting domain. Further provided are a pharmaceutical composition, a test kit, a kit of parts and an administration device containing the same, and a method of treating cancer by using the same. The concomitant use of the bispecific antibodies not only reduces the exhaustion of T cells, but also significantly facilitates tumor killing at a later stage. Moreover, the concomitant use of the bispecific antibodies, especially when targeting different epitopes of the same tumor-associated antigen or targeting different tumor-associated antigens, produces a strong synergistic killing effect. The use of the bispecific antibody combination and the pharmaceutical composition containing the same provides a potential clinical solution for effectively treating solid tumors.

Advantage is taken of the enhanced permeability and retention effect (EPR effect) to shield normal tissue from exposure to combinations of chemotherapeutic agents. Imaging agents that exhibit the enhanced permeability and retention (EPR) effect in solid tumors are useful in mimicking the behavior of chemotherapeutic or other drugs for treatment of said tumor conjugated to carriers of similar size and shape to the carriers of said imaging agents.

The invention relates to the technical field of solid tumor immunotherapy, in particular to an IL-2mRNA multichannel delivery method for solid tumor immunotherapy, which comprises the following steps: designing a DNA template, using a plasmid containing an IL-2 gene sequence such as human IL-2cDNA, adding a T7 promoter, a 5'untranslated region UTR and a 3 'UTR at two ends to enhance translation efficiency, carrying out in-vitro transcription through T7 RNA polymerase, and carrying out in-vitro transcription through T7 RNA polymerase. And adding a 5 '-end cap analogue such as CleanCapAG to realize co-transcription cap adding, and then preparing lipid nanoparticle LNP encapsulation and carrying out surface modification. According to the IL-2mRNA multi-channel delivery method for solid tumor immunotherapy, through multi-channel delivery design, targeting optimization and combined treatment cooperation, the toxicity problem of a traditional IL-2 therapy and the drug resistance of MHC-I defective tumors are remarkably solved, meanwhile, efficient conversion is achieved through existing equipment, IL-2 expression can be accurately regulated and controlled, the immune microenvironment can be remodeled, and the immunotherapy effect is good. Meanwhile, the system is compatible with various treatment means such as chemotherapy, radiotherapy and immune checkpoint inhibitors.

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 invention relates to a method or use for treating a solid tumor with the combined administration of a TROP2-targeting antibody-drug conjugate and a PD-1 antagonist.

The invention belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting cross binding of human and cynomolgus monkey CD46 and application of the single-domain antibody. The alpaca is utilized to generate the nanoscale antibody, the molecular weight of the nanoscale antibody is about 15 kDa, the nanoscale antibody can more efficiently penetrate solid tumor tissues or cross a blood brain barrier, and the binding efficiency of the antibody and a target spot is improved as much as possible. The 11 single-domain antibodies prepared by the invention have the specificity of resisting human and cynomolgus monkey CD46, the binding potency of the 11 single-domain antibodies is remarkably superior to that of an Anti-CD46 humanization antibody in the binding detection of CD46 target protein and CD46 overexpression cells, and the 11 single-domain antibodies can be used for treating tumors. Meanwhile, the single-domain antibody disclosed by the invention has cross-species cross binding capacity, can be directly used for preclinical pharmacodynamics and safety evaluation, does not need to develop a species-specific substitution antibody, and realizes'one target and double effects'.

The 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.