Probiotic Based Neoantigen Delivery for Cancer Immunotherapy

Methods for treating individuals at high risk of cancer recurrence or development using a personalized neoantigen immunogenic composition. The methods involve identifying individuals at risk based on risk stratification parameters, analyzing biological samples using multi-cancer detection tests, and administering a neoantigen immunogenic composition based on the test results. The composition is designed to elicit an immune response against specific cancer neoantigens, providing a treatment option for individuals who would otherwise receive a "watch and wait" approach.

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A method for designing a neoantigen vaccine that maximizes the likelihood of eliciting an immune response against cancer cells. The method involves simulating cancer cells based on patient data, predicting the likelihood of each neoantigen candidate eliciting an immune response, and selecting the optimal set of neoantigens using a constrained optimization algorithm. The algorithm minimizes the likelihood of no immune response across all cancer cells while maximizing the likelihood of immune response against each individual cancer cell.

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Method for selecting novel antigens for developing personalized anticancer vaccines by predicting and prioritizing tumor-specific neoantigens using machine learning models that integrate binding affinity and immunogenicity scores. The method involves constructing a prediction model using a database of known peptide-HLA interactions and then applying it to patient-derived tumor sequencing data to identify high-priority neoantigens. The selected neoantigens are then validated through functional assays to confirm their immunogenic potential.

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A method for treating cancer by modifying immune suppressor cells to include an innate immune effector, such as TRAIL, which enhances cell death of tumor cells. The modified cells, including regulatory T-cells and myeloid-derived suppressor cells, are administered to the patient to overcome immune suppression in the tumor microenvironment and improve the efficacy of cancer immunotherapy.

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Personalized bacterial cancer vaccines (PBCVs) that harness the immune system's potential to precisely and effectively manage cancer through targeted delivery of neoantigens to the gut microbiome. The approach combines patient-specific neoantigen selection from tumor cells with components of the patient's microbiome and immune system, utilizing an engineered bacterial system that releases these neoantigens in the gut environment. The PBCVs are engineered to express specific tumor antigens, which are then targeted by the patient's immune system to induce an immune response against cancer cells. This personalized approach enables the development of targeted cancer vaccines that can provide long-lasting immune memory and therapeutic effects.

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A pharmaceutical composition for treating cancer that contains a combination of microbial agents like Staphylococcus aureus, Bordetella pertussis, and Salmonella spp. along with polyinosinic acid, polycytidylic acid, and vitamins. The microbial agents stimulate the innate immune system, while the polynucleotides and vitamins enhance adaptive immune responses. This synergistic activation of both arms of the immune system aims to provide broad and potent anti-tumor activity, especially in "cold tumors" with low T cell infiltration.

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Immunostimulatory bacteria engineered to selectively target tumor-resident immune cells and deliver therapeutic products, such as RNAi or antibodies, to inhibit immune checkpoint molecules like TREX1, PD-L1, and VISTA. The bacteria, including strains of Salmonella, Shigella, and E. coli, are designed to accumulate in tumors and induce anti-tumor immune responses while minimizing collateral damage. They can be used in combination with conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, to enhance treatment efficacy.

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A pharmaceutical combination for cancer treatment comprising a recombinant Gram-negative bacterial strain and an immune checkpoint modulator (ICM), where the bacterial strain is genetically modified to express a heterologous protein fused to a bacterial effector protein delivery signal, and the combination provides a synergistic anti-tumor effect.

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Compositions and methods for treating ovarian cancer using neoantigens derived from tumor mutations. The neoantigens are encoded by polynucleotides that can be expressed in vectors, viruses, or self-replicating RNA molecules. These compositions can be used to induce an immune response against ovarian cancer cells, either alone or in combination with checkpoint inhibitors. The neoantigens are identified through bioinformatics analysis of ovarian cancer genomes and are shown to be immunogenic in preclinical models.

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Methods and compositions for treating breast cancer using neoantigens derived from estrogen receptor alpha (ERα) mutations. The neoantigens are identified through a screening process involving dendritic cell activation and T cell stimulation. T cells, including CAR T cells, TILs, and MILs, that recognize these neoantigens are used to treat ER-positive breast cancer, particularly in patients who have developed resistance to endocrine therapies. The approach leverages the unique mutation patterns of ERα in breast cancer to generate targeted immune responses against tumor cells.

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A method for selecting tumor-specific peptides for personalized cancer immunogenic compositions that provides coverage for heterogeneous malignancies. The method involves identifying tumor-specific neoantigens through high-throughput sequencing, predicting their presentation and immunogenicity, and selecting a subset of peptides that maximizes coverage across tumor subclones. The selected peptides are then formulated into a personalized immunogenic composition that elicits a targeted immune response against the subject's unique tumor mutations.

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Use of Enterococcus Lactis in preparation of a drug for treating melanoma, wherein the Enterococcus Lactis with preservation number of CCTCC NO: M20211220 has a significant inhibiting effect on the volume of melanoma, can inhibit the growing speed of melanoma, be used for treatment of melanoma, help to develop therapeutic drugs for melanoma, and have excellent application properties and wide market prospect.

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A cancer vaccine comprising genetically modified bacteria that home to tumors and express cancer-associated antigens, providing a targeted and adjuvant-enhanced immune response against cancer cells. The bacteria can be engineered to express specific antigens, and their ability to home to tumors enables them to deliver antigens directly to the tumor microenvironment. The vaccine can be administered in multiple cycles, with each cycle using a different strain of bacteria, to provide sustained immune activation against cancer cells.

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A cancer vaccine that utilizes non-genetically modified bacteria to present cancer-associated antigens on their outer surface. The bacteria are engineered to incorporate modified amino acids that can bind to cancer antigens through click chemistry reactions, enabling the antigens to be displayed on the bacterial surface without genetic modification. This approach leverages the natural immunogenicity of bacteria to stimulate an immune response against cancer cells.

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A Prevotella stercorea strain or its culture solution enhances immunity and increases the efficacy of immune checkpoint inhibitors in cancer treatment. The Prevotella stercorea strain increases T cell proliferation and IFN-γ secretion, and when combined with PD-1 inhibitors, significantly inhibits tumor growth and increases memory T cell proportions.

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A pharmaceutical composition that enhances the effect of immune checkpoint inhibitors against tumors and cancers by combining bacterial cells, culture supernatant, metabolites, and/or extracts of Ruminococcaceae enterobacterium with the inhibitors. The composition is produced by isolating and culturing the bacteria from intestinal contents of responders to immune checkpoint inhibitors, and administering the bacteria in combination with the inhibitors to activate anti-tumor immune responses.

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Engineered probiotics that colonize colorectal tumors and produce diagnostic and therapeutic molecules for cancer screening, prevention, and treatment. The probiotics comprise a synchronized lysis circuit that releases therapeutic agents in response to tumor presence, enabling non-invasive detection and treatment of colorectal cancer.

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Reducing the risk of cancer or an auto-immune disorder by identifying novel antigens that bind to a particular T cell receptor. The identification is performed using sequencing data obtained from a subject.

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Methods for treating or preventing cancer using personalized tumor vaccines based on neoantigens derived from chimeric RNA sequences. The methods involve identifying chimeric nucleotide sequences from cancer cells, extracting peptides from these sequences, and selecting immunogenic peptides that can elicit an immune response against cancer cells. The selected peptides are then used to develop tumor vaccines that can be broadly applicable to different patients suffering from the same cancer.

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A cancer immunotherapy that targets tumor-specific neoantigens, which arise from genetic mutations in cancer cells. The therapy comprises peptides, polynucleotides, and peptide binding agents that stimulate an immune response to neoepitopes, which are unique to the tumor. The therapy can be administered as a vaccine or through sequential immunization with longer and shorter peptides to enhance immune response.

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A modified BCG vaccine that elicits a targeted immune response against specific diseases, including cancer and infectious diseases. The vaccine comprises live attenuated Mycobacterium bovis (BCG) coated with a plurality of peptide antigens that are attached using a poly-lysine or poly-arginine linker. The peptide antigens can be derived from disease-specific antigens, tumor-associated antigens, or viral antigens, and can be used to elicit a specific immune response against the targeted disease. The vaccine can be administered intradermally, intranasally, or intratumorally, and can be used in combination with checkpoint inhibitors to enhance its therapeutic efficacy.

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A pharmaceutical composition for treating cancer comprising a gut bacterial lysate, wherein the lysate is derived from one or more species of Gram-positive and/or Gram-negative bacteria, and the composition further comprises a pharmaceutically acceptable carrier and/or excipient. The composition may be administered orally or parenterally, and may be used in combination with other cancer treatments, including immune checkpoint inhibitors, modified immune cells, and bispecific antibodies. The gut bacterial lysate may be derived from bacteria having genomic DNA with a CpG abundance substantially similar to that of a gut bacterium, or may comprise a Lipid A structure substantially similar to that of B. thetaiotaomicron.

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A method for identifying and targeting cancer-specific neoantigens for immunotherapy, using circulating tumor DNA (ctDNA) analysis to predict neoantigen prevalence and guide personalized vaccine composition. The method involves sequencing ctDNA to generate a numerical probability score of neoantigen presence, which is used to select and formulate a subject-specific vaccine. The approach enables non-invasive monitoring of tumor dynamics and neoantigen expression, facilitating adaptive immunotherapy strategies.

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T cell receptors (TCRs) that recognize neoantigens, which are tumor-specific antigens generated by non-synonymous somatic mutations. The TCRs can be used to treat cancer by targeting tumor cells that express these neoantigens. The TCRs can be administered alone or in combination with other cancer therapies, such as checkpoint inhibitors or targeted therapies. The TCRs can also be used to expand tumor-infiltrating lymphocytes (TILs) or chimeric antigen receptor (CAR) T cells in vitro before administration.

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A recombinant Gram-negative bacterial strain for delivering repeated domains of a heterologous protein or multiple domains of different heterologous proteins into eukaryotic cells. The strain is engineered to express a heterologous protein domain through the type III secretion system (T3SS), allowing for synchronized and homogenous delivery of protein domains into eukaryotic cells. The system enables the delivery of functional eukaryotic proteins, including apoptosis regulators and cell cycle regulators, into living animals for therapeutic purposes.

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A method for selecting tumor-specific neoantigens for personalized cancer immunotherapy. The method involves sequencing tumor DNA and RNA to identify neoantigens, predicting their immunogenicity, and evaluating their expression levels and tumor fraction. The selected neoantigens are then formulated into a subject-specific immunogenic composition for cancer treatment.

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A method for enhancing the efficacy of chemotherapy in cancer treatment by administering live attenuated Gram-negative bacteria in a first treatment phase, followed by chemotherapy in a second treatment phase. The bacteria induce an immune response that primes the body to respond more effectively to the chemotherapy, reducing tumor burden and metastasis while minimizing normal tissue damage.

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Personalized cancer vaccine comprising a unique combination of tumor-specific neoantigen peptides, including long and short peptides, and an adjuvant, optionally with helper peptides and tumor-specific frameshift peptides. The vaccine is designed to target cancer-specific mutations and induce a specific immune response against the tumor.

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A method for ranking tumor-specific neoantigens for personalized cancer immunotherapy. The method identifies somatic mutations in a tumor, generates short and long neoantigen candidates from these mutations, and evaluates each candidate using a quality score that incorporates predicted presentation probability, binding affinity, and immunogenic response. The candidates are then ranked by descending quality score, with the top-ranked neoantigens selected for inclusion in a personalized immunogenic composition.

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A highly attenuated Listeria monocytogenes (Lm) strain that can be used as a vaccine vector to treat cancer. The Lm strain is modified to express tumor antigens fused to a derived Listeriolysin O (LLO) protein. The LLO protein is a virulence factor that allows Lm to escape from host cells. By fusing tumor antigens to LLO, the modified Lm strain can express and present tumor antigens to activate T cells. The Lm strain is attenuated by knocking out virulence genes and replacing them with an independent plasmid for antigen expression.

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Bacterial strains of the genus Enterococcus, particularly Enterococcus gallinarum, Enterococcus casseliflavus, and Enterococcus hirae, are used to enhance the effectiveness of neoadjuvant and/or adjuvant cancer therapies. These strains increase the sensitivity of cancer cells to cytotoxic effects of chemotherapy, radiation, and other treatments, leading to improved clinical and pathological response rates. The strains can be administered orally or through other routes, and can be lyophilized for stability and convenience.

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Personalized tumor vaccine for cancer immunotherapy that leverages phagocytosis stimulating agents and immunostimulatory adjuvants to direct an immune response against subject-specific cancer cells. The vaccine comprises a phagocytosis stimulating agent, such as mannan, conjugated to a biocompatible anchor, an immunostimulatory adjuvant, such as R-848 or poly(I:C), and attenuated cancer cells. The vaccine activates an immune response by stimulating phagocytosis and activating immune cells, including dendritic cells and T cells, to target and eliminate subject-specific cancer cells.

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Using specific bacteria and prebiotics to treat cancer by modulating the gut microbiome. The disclosure involves administering certain bacteria and prebiotics to cancer patients to alter their gut microbiome composition and improve cancer treatment outcomes. The bacteria include Oscillibacter valericigenes, Acetatifactor muris, Alistipes putredinis, Alistipes finegoldii, Clostridium clostridioforme, Lactobacillus animalis, Lactobacillus murinus, Bacteroides massiliensis, Bacteroides sartorii, Muribaculum intestinale, Parasutterella excrementihominis, Clostridium methylpentosum, and Bacteroides rodentium. The prebiotics include those that promote the growth of these bacteria.

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A method for enhancing the efficacy of immune checkpoint inhibitors in cancer treatment by administering a specific bacterium, Alistipes finegoldii, in combination with the inhibitors. The bacterium, which is an endogenous intestinal commensal, is administered orally and stimulates an anti-tumor immune response that complements the action of the immune checkpoint inhibitors. The combination therapy has been shown to significantly enhance the therapeutic effect of the inhibitors, including improved progression-free survival and tumor response rates, while maintaining a favorable safety profile.

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A cancer immunotherapy that enhances epitope processing and presentation to stimulate an immune response. The therapy comprises a synthetic peptide comprising an epitope presented by a class I MHC or a class II MHC of an antigen presenting cell (APC), where the epitope is derived from a tumor-specific antigen or neoepitope. The peptide is engineered to improve epitope processing and presentation, enabling more efficient activation of antigen-specific T cells. The therapy can be administered as a vaccine or used to stimulate T cells ex vivo for adoptive transfer.

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A method of increasing effectiveness of an immune checkpoint inhibitor in a subject comprising administering the inhibitor and modulating the subject's intestinal microbiota by increasing beneficial bacteria such as Ruminococcus torques, Blautia wexlerae, and Eubacterium rectale, and decreasing detrimental bacteria such as Bacteroides massiliensis and Prevotella copri. The method predicts responsiveness to the inhibitor based on the presence or absence of these bacteria in the subject's stool sample.

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A system and method for assessing and reducing cancer risk by modulating stress response in the host's microbiota. The system prepares a knowledgebase of microbes and microbial functions through whole-genome sequencing, functional annotation, and machine learning-based prediction models. The knowledgebase identifies good and bad microbes based on their competitive traits, enabling personalized cancer risk assessment and management through targeted probiotic and prebiotic interventions. The method employs fasting-induced stress to activate anti-cancer microbial responses, with prebiotic support accelerating the process.

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Compositions and methods for treating cancer using live, non-pathogenic bacteria and bacterial spores that modulate the gut microbiome to enhance cancer treatment efficacy. The compositions can be administered as a mono-therapy or in combination with conventional cancer therapies, including checkpoint inhibitors, chemotherapy, and radiation therapy. The bacteria and spores can be isolated from healthy donors or engineered to produce specific therapeutic effects, and can be formulated for delayed release or implantation into the gut.

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A cancer treatment method that combines a shared neo-epitope vaccine with a personalized neo-epitope vaccine to induce a targeted immune response against cancer cells. The shared vaccine contains neo-epitopes common to multiple cancer types, while the personalized vaccine contains neo-epitopes specific to the individual patient's cancer. Both vaccines exclude neo-epitopes that could engage regulatory T cells or other detrimental immune cells, thereby enhancing the treatment's efficacy and safety.

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Immunostimulatory bacteria engineered to enhance anti-tumor responses through targeted modifications in their genetic makeup. These bacteria contain plasmids encoding therapeutic products, including anti-cancer proteins, that are specifically expressed in tumor-resident immune cells. The modifications include genetic deletions or disruptions of critical components of the outer membrane lipopolysaccharide biosynthesis pathway, as well as alterations in flagellar structure, asparaginase expression, and immune cell activation pathways. These bacteria retain their ability to infect and survive within tumor microenvironments while selectively expressing therapeutic proteins that stimulate anti-tumor immune responses.

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Generic microorganisms that can be used in conjunction with conventional cancer therapies, such as surgery, chemotherapy, targeted therapies, radiation therapy, tomotherapy, immunotherapy, cancer vaccines, hormone therapy, hyperthermia, stem cell transplant (peripheral blood, bone marrow, and cord blood transplants), photodynamic therapy, therapy, and blood product donation and transfusion, and oncolytic viruses. The microorganisms are selectively and locally producing one or more anti-cancer molecules at the tumor site, and have the added advantage of being able to activate an intratumoral immune response.

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Methods and compositions for identifying and utilizing neoantigens in cancer immunotherapy. The methods involve whole exome sequencing of cancer cells, filtering out common mutations, and creating single-mutation peptide constructs to identify neoantigens recognized by T cells. The identified neoantigens can be used to engineer T cells with chimeric antigen receptors (CARs) or T cell receptors (TCRs) for adoptive transfer into cancer patients.

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Epithelial cells that can be used in cancer therapy. The cells include a transposable element (TE)- exon fusion transcripts, nucleic acids, vaccines, antibodies and immune cells that can be used in cancer therapy.

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Tumor neoantigens derived from junctions between transposable elements (TEs) and exons (JETs) that are uniquely expressed in cancer cells and not in normal tissues. These neoantigens are identified through a method that selects for peptides encoded by fusion transcripts containing TE-exon junctions. The JET-derived neoantigens exhibit high immunogenicity and are suitable for use in cancer vaccines, adoptive cell therapy, and other immunotherapies.

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Methods and compositions for preventing, treating, and diagnosing cancer using frameshift (FS) neoantigens generated by errors in RNA processing. FS neoantigens are created by mis-splicing of exons and mis-transcription of microsatellites, resulting in predictable sequences that can be represented on a peptide array. The array can detect antibody responses to FS neoantigens in patients, enabling the development of cancer vaccines that can be broadly protective or tailored to specific tumor types.

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A cancer treatment and virus protection method that uses an attenuated bacteria expressing an mRNA-mediated virus vaccination antigen to induce a strong immune response against tumors and viruses. The bacteria, engineered to express a viral antigen, is administered to a subject in an amount effective to treat the tumor and protect against the virus, addressing challenges in traditional cancer immunotherapy and virus vaccination.

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A novel application of Enterococcus lactis as a tumor suppressor for preventing or treating various cancers, including colorectal, liver, pancreatic, breast, kidney, and lung cancers. The Enterococcus lactis strain MNC-168 induces differentiation of immune cells, including macrophages and dendritic cells, into pro-inflammatory phenotypes that secrete cytokines and chemokines to combat tumors. The strain's ability to survive in the gastrointestinal tract and induce immune responses makes it a promising candidate for cancer immunotherapy.

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A method for predicting tumor-specific neoantigen immunogenicity by jointly predicting MHC class I or II binding affinity and presentation likelihood, enabling the identification of neoantigens with high positive predictive value for personalized cancer vaccines. The method combines machine learning models to accurately predict neoantigen immunogenicity, overcoming limitations of existing approaches.

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A composition comprising specific intestinal bacteria, such as Alistipes shahii, Eubacterium ramulus, and Prevotella ruminicola, for promoting the proliferation of TCR γδ+ T cells and accumulation of CD8+ cytotoxic T lymphocytes in tumor microenvironments, thereby enhancing anti-tumor immune responses. The composition can be used to prevent and treat various cancers, including liver cancer.

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Combination cancer therapy using an immune signaling pathway modulator and a bacterial fluid of healthy human gut flora, specifically Bifidobacterium animalis subsp. Lactis, to enhance tumor immunotherapy response. The probiotic is administered alone or in combination with immune checkpoint inhibitors to improve treatment outcomes in gastrointestinal and breast cancers.

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