68 results about "Tumor response" patented technology

Radiotherapy is the most widely used and effective anti-tumor therapy, however it can damage healthy tissues surrounding the tumor. One approach to reducing damage to healthy tissue involves irradiation at dose rates far exceeding those currently used in clinical contexts reduces radiation-induced toxicities while maintaining an equivalent tumor response. This is known as the FLASH effect. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy (FLASH-RT) is still undetermined; multiple hypotheses have been suggested by linking the high dose rate to rapid oxygen depletion, immune response, reduction of peroxyl radical lifetime, preservation of normal tissue stem cells, etc. While effective, proton therapy is underutilized, contributing to fewer than 2% of all external beam radiation treatments. To overcome this shortcoming, provided are methods which utilize the highest energy layer and a universal range shifter (URS) to facilitate rapid spot arc therapy (RAPIDSPARC™).

The present invention provides variant forms of anti-CTLA-4 antibodies, such as ipilimumab, that preferentially bind to CTLA-4 at low pH. Such antibody variants exhibit preferential activity in the tumor microenvironment, an enhanced ratio of anti-tumor response to side-effects, and an enhanced therapeutic index.

The present invention relates to antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and / or expand T effector cell populations or function. For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

This application relates to the field of tumor treatment technology, specifically to a drug combination and evaluation method for improving the sensitivity of MSS CRC to anti-PD-1 / PD-L1 therapy. The drug combination comprises vancomycin and an immune checkpoint inhibitor. Vancomycin is used to remodel the gut microbiota and reduce L-asparagine levels; the immune checkpoint inhibitor is used to activate CD8. + T-cell anti-tumor response. By combining vancomycin with immune checkpoint inhibitors, the antigen-presenting capacity of dendritic cells is enhanced, thereby increasing the sensitivity of MSS CRC to anti-PD-1 or anti-PD-L1 immunotherapy. This application focuses on the upstream initiation link of gut microbiota-metabolites-dendritic cells-immune activation, relieving the inhibition of dendritic cell antigen presentation by L-asparagine and enhancing CD8+. + T cell activation and tumor immune response enhance the sensitivity of MSS-type colorectal cancer to anti-PD-1 / PD-L1 therapy.

To provide biomarkers for predicting tumor response to and toxicity of immunotherapy.SOLUTION: The invention is directed to biomarkers for predicting a patient's response, both therapeutic and toxic, to immunotherapy. The invention is based, in part, on the discovery that cancer patients carrying one or more specified mutations in their genome may respond to treatment with an immune modulating agent more effectively than other cancer patients, for example, patients homozygous for the wild-type allele. The invention is also based, in part, on the discovery that cancer patients carrying one or more specified mutations in their genome may respond to treatment with an immune modulating agent less effectively than other patients, for example, cancer patients homozygous for the wild-type allele.SELECTED DRAWING: None

The application discloses application of ginsenoside Rf in preparation of an enhancer of a PD-1 inhibitor antitumor drug, and the ginsenoside Rf has the effects of improving a PD-1 inhibitor antitumor response rate, prolonging a survival period, and reducing toxicity, and has a significant advantage in enhancing PD-1 inhibitor treatment of tumors.

This invention relates to an oral nanomedicine antigen delivery system and its construction method and application, belonging to the field of oral nanomaterials technology; the construction method includes the following steps: (1) preparation of OM nanoparticle suspension; (2) preparation of cationic liposome suspension; (3) preparation of cationic liposome suspension loaded with OM / BF; (4) construction of oral nanomedicine antigen delivery system. This invention breaks through multiple barriers in the gastrointestinal tract, improves drug bioavailability, and achieves precise immune tracking through the OVA tumor antigen model, simulating in vivo anti-tumor CTL response, thereby exerting anti-tumor effects synergistically at the cellular, tissue, and immune levels, effectively solving the problems of poor water solubility and low delivery efficiency of the active ingredient bufotoxin in traditional Chinese medicine. At the same time, through macrophage-mediated immune regulation and precise drug release, it improves targeting and treatment efficiency, opening up a new avenue for tumor immunotherapy with oral nanomedicine.

A multi-specific antibody contains at least one binding site for a cell specific antigen and at least one binding site for a tumor-reactive lymphocyte antigen and a multi-specific antibody including an IgG antibody or fragment thereof that binds to a first antigen; and at least one scFv antibody that binds to a second antigen that is different from the first antigen and is linked to a C terminus of at least one light chain or heavy chain of said IgG antibody or fragment. The multi-specific antibody reversibly binds to at least one of the cell specific antigen and tumor-reactive lymphocyte antigen or the first antigen and the second antigen with a greater affinity at an aberrant condition than at a normal physiological condition. Conjugates of the multi-specific antibodies and methods for generating the multi-specific antibody are also provided.

Disclosed herein is a method for ex vivo expanding tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). The method involves culturing tumor fragments from the subject in a culture medium containing IL-2 and a 41BB agonist in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity. Also disclosed is a method for treating a tumor in a subject that involves treating the subject with nonmyeloablative lymphodepleting chemotherapy, and administering tumor-infiltrating lymphocytes expanded by the disclosed methods.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.

This invention discloses a STAT3-mutated cell product and its uses, belonging to the interdisciplinary field of genetic engineering and tumor immunotherapy. Through saturation mutation screening, this invention is the first to discover that STAT3 gain-of-function mutations promote CAR-T anti-tumor responses. Furthermore, through cell and animal experiments, it is demonstrated that activating STAT3 can alleviate CAR-T cell immune exhaustion and significantly enhance the in vivo and in vitro killing ability of CAR-T cells against tumor cells, thereby improving the efficacy of anti-tumor therapy. This invention provides a new therapeutic target and strategy for the field of tumor immunotherapy, possessing significant scientific and clinical application value.

Provided are systems and methods of enhancing tumor-reactive immune populations such as tumor infiltrating lymphocytes from patient-derived organoids. Also, provided herein are systems and methods of expanding and reprogramming tumor-reactive immune populations such as tumor infiltrating lymphocytes to improve anti-tumor activity. The systems and methods described herein can be used for adoptive cell therapy.

An adaptive radiotherapy system (100) with biophysical real-time monitoring of the tissue response, wherein the system (100) comprises: a module (1) for real-time biophysical tissue response monitoring, configured to acquire live data on the physiological response and tissue response from a treatment area of ​​a patient during irradiation; a module (2) for localizing patient anatomy and motion detection, configured to detect position changes, organ movements and target shifts in real time; an engine (3) for adaptive treatment planning and dose recalculation, configured to dynamically update a radiotherapy treatment plan based on data received from the module (1) for real-time biophysical monitoring of tissue response and from the module (2) for localizing patient anatomy and motion detection; an engine for predictive modeling of tissue response (4) configured to estimate short-term tissue response, tumor response and normal tissue tolerance using patient data from current and previous sessions; an interface for controlling and modulating the beam (5) which is functionally coupled to a radiation delivery device and configured to modify one or more beam parameters in real time; a safety check and treatment lock control (6) configured to compare current treatment conditions with one or more allowable thresholds and selectively interrupt, stop, or release radiation delivery; and a module (7) for clinical review, data logging and treatment evaluation, configured to store treatment response data, generate session-related adjustment protocols and provide one or more recommendations for subsequent fractions, wherein the system (100) adaptively modifies the radiation output in response to continuously monitored biophysical tissue conditions of the patient.

Radiotherapy is the most widely used and effective anti-tumor therapy, however it can damage healthy tissues surrounding the tumor. One approach to reducing damage to healthy tissue invoves irradiation at dose rates far exceeding those currently used in clinical contexts reduces radiation-induced toxicities while maintaining an equivalent tumor response. This is known as the FLASH effect. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy (FLASH-RT) is still undetermined; multiple hypotheses have been suggested by linking the high dose rate to rapid oxygen depletion, immune response, reduction of peroxyl radical lifetime, preservation of normal tissue stem cells, etc. While effective, proton therapy is underutilized, contributing to fewer than 2% of all external beam radiation treatments. To overcome this shortcoming, compact radiotherapy systems are provided that incorporate multi-function components, reducing bot equipment size and expense.

The application discloses a paclitaxel treatment response prediction method and system for triple-negative breast cancer patients, and the method comprises the following steps: obtaining single-cell transcriptome data, bulk transcriptome data and paclitaxel sensitivity data of triple-negative breast cancer patients before and after treatment and preprocessing; constructing a regression model of immune microenvironment and tumor response, calculating the response score of immune cell subgroups, screening key immune cell subgroups related to paclitaxel treatment response, performing differential expression analysis on the pre-treatment sample, constructing a paclitaxel IC50 prediction model, and dividing the sample into a high-sensitivity group and a low-sensitivity group; constructing a treatment response prediction model and outputting a prediction result. The technical scheme integrates the dynamic changes of the immune microenvironment, the transcriptome characteristics and the drug sensitivity data, realizes accurate prediction of the paclitaxel treatment response of the triple-negative breast cancer patients before treatment, and provides a scientific basis for formulating an individualized treatment plan.

This invention discloses a high-load XOR tumor-targeting therapy nanoplatform based on ROS activity and its applications, belonging to the field of nanobiomaterials. This high-load XOR tumor-targeting therapy nanoplatform, using a zeolite imidazole framework-8 (ZIF-8) as a carrier, contains xanthine oxidoreductase (XOR) with cellular enzymatic activity. It possesses the ability to target tumor cells and induce intracellular reactive oxygen species (ROS), leading to tumor cell death. Induction of intracellular ROS in tumor macrophages (TAMs) also supports the differentiation of macrophages into M1 types. ROS-induced apoptosis in tumor cells produces a series of tumor-associated antigens, which further promotes the infiltration and activation of macrophages in the tumor microenvironment. This, in turn, leads to increased infiltration of CD8+ T cells in the tumor, whose cytokine profile shows cytotoxic effects, indicating successful induction of an adaptive anti-tumor response. This novel nanomaterial offers a promising new strategy for the immunotherapy of gastric diseases.

The present invention relates to a tumor-reactive T cell composition obtained by expansion from a patient sample, wherein upon stimulation with tumor cell antigens, the proportion of CD8+CD137+ cells among CD45+ cells in the composition is at least greater than 25%, and / or the proportion of CD45RA+CD62L+ cells in the composition is at least greater than 30%. The present invention further relates to a method for obtaining a tumor-reactive T cell composition by expansion from a patient sample. Tumor-reactive T cells in the composition of the present invention have a high total count, a long lifespan, a high viability rate, and a potent tumor-killing capacity, thereby providing a basis for the use of the composition in tumor therapy.

Provided herein are methods of isolating and expanding a population of tumor reactive lymphocytes (TRLs) from a fluid sample of a subject in need thereof. In some embodiments, methods of isolating and expanding a population of TRLs comprise flowing the TRLs across a magnetic capture zone of a microfluidic device. In some embodiments, expanding a population of TRLs comprises exposing TRLs to a culture condition (e.g., cytokine environment) during expansion that modifies the rapidity or robustness of expansion or the purity, sensitivity (e.g., to cytokines), or memory phenotype of TRLs after expansion. Also provided herein are methods of administering a population of TRLs to a subject in need thereof. Also provided herein are compositions comprising therapeutically enhanced TRLs.

The invention relates to siRNA as well as a conjugate and application thereof, and belongs to the technical field of molecular biology and biological medicine. The siRNA comprises a positive-sense strand and an antisense strand. The conjugate comprises an aptamer and siRNA (small interfering Ribonucleic Acid). The siRNA and the conjugate provided by the invention are good in targeting property and high in safety, enter cancer cells (such as liver cancer cells) without the help of an exogenous transfection agent, and realize efficient knock-down of an immune checkpoint Nectin-2, so that the anti-tumor reaction of T cells is activated, and the siRNA and the conjugate are used for precise immunotherapy of tumors (such as liver cancer). The conjugate provided by the invention can be autonomously delivered to tumor cells without a transfection agent, quickly enters cytoplasm of the tumor cells without the help of lipidosome, polymer or viral vector, and generates a functional effect. The delivery strategy is high in safety, has unique practical value, and is different from a current mainstream delivery system in the RNA interference field.

Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Provided herein are methods for making a tumor infiltrating lymphocytes (TILs) product enriched with neoantigen-reactive T cells (NARTs), comprising: generating a plurality of TIL populations by fractioning a tumor sample; selecting one or more TIL populations enriched with NARTs by profiling the plurality of TIL populations using multiplex digital PCR (dPCR); and preferentially expanding the NARTs by co-culturing the one or more TIL populations enriched with NARTs with tumor cells from the tumor sample in a first cell culture medium to generate the TIL product enriched with NARTs. Further provided is a method for assessing tumor reactivity of a population of T cells, comprising measurement of the expression level of a panel of target genes of the population of T cells.

Provided herein are methods for producing tumor-reactive T cells, including ex vivo enrichment and expansion of cells secreting chemokine (C-X-C motif) ligand 13 (CXCL13); cells surface-positive for C-X-C chemokine receptor type 5 (CXCR5); and / or cells surface-positive for one or more of CD39, PD-1, and TIGIT. Also provided are T cell populations generated by the methods described herein, and pharmaceutical compositions thereof. TIFF2023516636000026.tif24170

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 relates to an oral nano traditional Chinese medicine antigen delivery system as well as a construction method and application thereof, and belongs to the technical field of oral nano materials. The construction method comprises the following steps: (1) preparing an OM nanoparticle suspension; (2) preparing a cationic liposome suspension; (3) preparing an OM / BF loaded cationic liposome suspension; and (4) constructing an oral nano traditional Chinese medicine antigen delivery system. According to the invention, multiple barriers of gastrointestinal tracts are broken through, the bioavailability of drugs is improved, precise immune tracking is realized through an OVA tumor antigen model, and in-vivo anti-tumor CTL reaction is simulated, so that an anti-tumor effect is synergistically exerted on three levels of a cell level, a tissue level and an immune level; according to the preparation method, the problems of poor water solubility and low delivery efficiency of bufalin serving as a traditional Chinese medicine active ingredient are effectively solved, meanwhile, through macrophage-mediated immunoregulation and accurate drug release, the targeting property and the treatment efficiency are improved, and a new way is opened up for tumor immunotherapy of oral nano traditional Chinese medicines.

The present application relates to the field of biotechnology and cell therapy, in particular to a VHH antibody, CAR-NK cell and application.Under the condition of gradient progression of effector-target ratio, based on the luciferase method detection, it is found that the cytotoxicity decreases with the decrease of effector-target ratio, the BCMA-CAR-NK cell corresponding to the four VHH antibodies can effectively kill MM.1S, and the killing ability is significantly stronger than that of the control group.The above proves that hBCMAnb-CAR-NK has the tumor response reaction specific to BCMA.

This invention provides a dual-wavelength confocal superlens and its design method, as well as a photoacoustic imaging method and system, belonging to the field of optical lens technology. The invention provides a design method for a dual-wavelength confocal superlens that can use two different wavelengths of light to visualize cancer cells and normal tissues. Normal cells and cancer cells absorb energy from the two different wavelengths, causing them to heat up and expand. After cooling, they emit ultrasonic waves, which are then collected by an ultrasonic transducer. Finally, photoacoustic imaging is achieved through calculation. This invention aims to enhance photoacoustic imaging contrast while avoiding the risks of invasive procedures. The dual-wavelength design provides multiple contrast mechanisms, allowing for the comparison of various tissue features during the same imaging process, enhancing the detection capability of lesions, and effectively reducing the influence of noise in the photoacoustic signal. This invention can be applied to early cancer detection and can also be used to monitor tumor response during treatment and evaluate treatment effectiveness.

The invention belongs to the technical field of medical treatment, and discloses an initial non-resectable hepatocellular carcinoma postoperative drug-free monitoring method based on complete pathology remission, and the method comprises the following steps: selecting a patient; all patients are subjected to systemic treatment or combined transarterial treatment; dosage adjustment and temporary interruption of treatment are allowed according to adverse reaction conditions; the transcatheter treatment comprises transcatheter arterial chemoembolization TACE and hepatic arterial perfusion chemotherapy HAIC; in assessing the tumor response, contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) is used every 6 to 8 weeks, based on the mRECIST and RECIST 1.1 criteria; postoperative adjuvant therapy is usually started 4-8 weeks after an operation, and is usually based on a preoperative transformation treatment scheme; the adverse reactions are evaluated by comparing the baseline value changes during the first post-operative follow-up with the subsequent follow-up.

The present invention provides a method for inducing peripheral blood CX3CR1+ potentially tumor-reactive T cells. The present invention provides an optimized hot and cold ablation method, which effectively increases the level of potentially tumor-reactive T cells in the peripheral blood of a test animal, thereby improving anti-tumor immune response. The present invention further provides a tumor-reactive T cell population prepared by means of a hot and cold ablation method.