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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