162 results about "Tumor response" patented technology

The present invention provides a tumor neoantigen vaccine system specifically marking a heterologous protein, and a use thereof. The vaccine system is composed of a heterologous protein mRNA vaccine and a recombinant oncolytic virus; the heterologous protein mRNA vaccine is used to induce an organism to generate heterologous protein-specific memory T cells, and the recombinant oncolytic virus is used to promote a tumor to express microorganism-derived tumor neoantigens. When pre-immunized memory T cells detect these marked specific neoantigens, the tumor expressing the neoantigens is quickly activated and killed, the release of tumor autoantigens is promoted, dendritic cells phagocytize antigens to further initiate an anti-tumor response, and a systemic anti-tumor immune effect is activated by means of antigenic epitope spreading.

Provided herein are methods for one or more of a) modulating an immune response to a tumor cell in a patient, b) treating cancer in a cancer patient; or c) eliciting an anti-tumor response in a patient, comprising modulating the expression or activity of Junction Adhesion Molecule Like (JAML).

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 invention discloses an MAGE-A10 specific T cell receptor (MAGE-A10TCR) and an application of the MAGE-A10 specific T cell receptor in immunotherapy, and belongs to the technical field of tumor immunotherapy. The MAGE-A10TCR is screened from a tumor reactive T cell of an HCC patient, can specifically recognize an MAGE-A10 antigen and is used for constructing the MAGE-A10TCR-T cell, and a cytotoxicity test shows that the MAGE-A10TCR-T cell has a clearing effect on the HCC cell.

The invention belongs to the technical field of tumor reactive T cell identification, and particularly relates to a pancreatic cancer tumor reactive CD8 + T cell identification method based on 10X single cell transcriptome sequencing combined with deep learning. According to the scheme, the method comprises the following steps: 1, carrying out single cell transcriptome sequencing on CD8 + T cells of a pancreatic cancer sample; 2, carrying out single cell transcriptome sequencing on the separated CD8 + T cells; step 3, screening characteristic variables; 4, training a deep learning model, wherein the model learns and identifies transcriptome characteristics of pancreatic cancer tumor reactivity and non-specific CD8 + T cells by using characteristic variables; 5, the accuracy, stability and generalization ability of the model are evaluated, and by means of the scheme, a set of tumor reactive CD8 + TILs identification process adopting the deep learning method is developed and verified.

The invention provides an improved in-vitro amplification method of tumor infiltrating lymphocytes. Specifically, the method for preparing the tumor infiltrating lymphocyte (TIL) comprises the following steps: (S1) providing a tumor tissue; (S2) carrying out fragmentation treatment on the tumor tissue to obtain tumor fragments; (S3) pre-culturing the tumor fragments by using a starting culture medium to obtain a first culture mixture; (S4) determining the first culture mixture so as to screen out the tumor reactive TIL; (S5) performing multiplication culture on the tumor reactive TIL by using an amplification culture medium to obtain a second culture mixture; and (S6) isolating or recovering tumor infiltrating lymphocytes (TIL) from the second culture mixture. The invention also provides the high-tumor-reactivity TIL prepared by the method and application of the high-tumor-reactivity TIL.

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.

The preset disclosure provides methods of culturing TILs by first culturing a tumor sample in a first expansion medium, wherein the first expansion medium comprises a CD3 agonist and APCs at a first ratio (a "first REP step"); and culturing the TILs from first REP step in a second expansion medium, wherein the second expansion medium comprises a CD3 agonist and APCs at a second ratio (a "second REP step"). In some aspects, the methods disclosed herein enhance expansion of CD8+ TILs, relative to CD4+ TILs. In some aspects, the methods further increase the number of less-differentiated cells, e.g., less-differentiated TILs, in the population of cells. In some aspects, the methods disclosed herein enrich for tumor-reactive, e.g., tumor specific, TILs such that clonal diversity is preserved. In some aspects, the cells, e.g., the TILs, are administered to a subject in need thereof.

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 a novel therapeutic strategy for treating cancers expressing embryonic antigens.SOLUTION: The inventors have developed a metastatic 4T1 breast tumor model in BALB / c mice. The inventors have showed that vaccination with xenogeneic embryonic stem cells in combination with valproic acid (VPA) generates a higher antitumor response against a breast cancer and inhibits metastasis development. The inventors have demonstrated that these responses are only achieved by the addition of valproic acid in a therapeutic regimen compared to the use of ESC or iPSC alone. Thus, the inventors provide a novel therapeutic strategy for treating cancers expressing embryonic antigens. The present invention therefore relates to a method for treating a subject suffering from cancer, comprising the steps of administering to the subject simultaneously, separately or sequentially a therapeutic amount of i) a population of pluripotent cells and ii) a compound selected from the group that activates MHC expression as a combined preparation.SELECTED DRAWING: None

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

Provided herein are methods of for enhancing or inducing an anti-tumor response or treating an autoimmune disorder by administering a therapeutically effective amount of an inhibitor of NAC 1. Also, provided herein are methods of enhancing effectiveness of a vaccine in a subject by administering to the subject a therapeutically effective amount of an inhibitor of NAC 1. Inhibitors of NAC1 can include a chemical agent, such as a composition containing NIC3, or a biological agent that inhibit the function of NAC1 protein, such as an isolated antibody or its binding fragment thereof that binds to NAC1. Inhibitors of NAC 1 can include a biological agent that reduces the expression of NAC1 gene, such as a NAC 1-targeted siRNA administered as a nanoliposome or a CRISPR / Cas-based genome editing composition targeting the NAC1 Gene.

The present disclosure provides interferon receptor agonists with improved safety profile and therapeutic index. The interferon receptor agonists are weakened by masking and / or reducing receptor binding as compared to the wild-type interferon. The IFN receptor agonist optionally further comprises a targeting moiety, e.g., a targeting moiety that recognizes tumor or immune cell associated antigens and directs the interferon receptor agonist to a tumor site and / or tumor reactive immune cells. The disclosure further provides pharmaceutical compositions comprising the interferon receptor agonists and methods of using the interferon receptor agonists in therapy, as well as nucleic acids encoding the interferon receptor agonists, recombinant cells expressing the interferon receptor agonists, and methods of producing the interferon receptor agonists.

The present invention relates to tumor-specific immune cell markers and their uses. Specifically, an immune cell marker combination is provided, comprising: (1) an immune cell activation marker, and (2) an immune cell inhibition marker, optionally further comprising (3) an intracellular marker, and / or (4) a tissue-resident memory marker. The marker combination of the present invention can more accurately identify and enrich tumor-specific immune cells, and the enriched cell population has better tumor reactivity and tumor killing function.

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.

The invention is directed to biomarkers for predicting a patient's response, both therapeutic and toxic, to immunotherapy.

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.

Provided herein are methods for manufacturing of tumor reactive T cells that includes ex vivo enrichment of, 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 one or more of CD39, PD-1 and TIGIT. Also provided are populations of T cells produced by methods described herein and pharmaceutical compositions thereof.

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.

Methods to treat cancer in a subject comprising administering to the subject a therapeutically effective amount of T-cells of the subject having increased IRF4 polypeptide expression compared to a control are disclosed. Also disclosed are methods of increasing tumor reactivity of a T-cell by increasing IRF4 polypeptide expression, and methods to predict the likelihood that a subject having cancer will respond therapeutically to administered T-cells having increased IRF4 polypeptide expression. Also disclosed are compositions comprising a T-cell and a viral vector encoding an IRF4 polypeptide. The compositions are methods are useful for treating numerous cancers in which higher level expression of IRF4 in T-cells would be beneficial. In some embodiments, activated tumor-specific T-cells having increased IRF4 expression have greater infiltration in tumors and enhanced local immunological responses.

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.

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.

The invention discloses a method for efficiently constructing a personalized pancreatic cancer organoid and screening a tumor reactive TCR (T cell receptor), which comprises the following steps: transferring RSPO1 and WNT3A genes into the pancreatic cancer organoid, and inducing expression and secretion of RSPO1 and WNT3A in the organoid by adding Dox (doxycycline). The pancreatic cancer antigen tumor reactive TCR can be screened from the PBMC of a pancreatic cancer patient by using the constructed transgenic organ.