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33 results for “tumor associated antigens”
Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs)
<p><strong><span>Background: </span></strong><span>We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP).</span></p> <p><strong><span>Method: </span></strong><span>A library of >100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8+ T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n=10) and cancer patients (n=16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA.</span></p> <p><strong><span>Results: </span></strong><span>A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA.</span></p> <p><strong><span>Conclusions: </span></strong><span>Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth (“natural anti-cancer vaccination”). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.</span></p>
MOLECULAR MIMICRY BETWEEN TUMOR ASSOCIATED ANTIGENS AND MICROBIOTA-DERIVED EPITOPES.
<p><strong>Background: </strong>The gut microbiota profile is unique for each individual and are composed by different bacteria species according to individual birth-to-infant transitions. In the last years, the local and systemic effects of microbiota on cancer onset, progression and response to treatments, such as immunotherapies, have been extensively described. Here we offer a new perspective, proposing a role for the microbiota based on the molecular mimicry of tumor-associated antigens by microbiome-associated antigens.</p> <p><strong>Methods:</strong> In the present study we looked for homology between published TAAs and non-self microbiota-derived epitopes. Blast search for sequence homology was combined with extensive bioinformatics analyses.</p> <p><strong>Results:</strong> Several evidences for homology between TAAs and microbiota-derived antigens have been found. Strikingly, three cases of 100% homology between the paired sequences has been identified. The predicted average affinity to HLA molecules of microbiota-derived antigens is very high (<100nM). The structural conformation of the microbiota-derived epitopes is, in general, highly similar to the corresponding TAA. In some cases, it is identical and contact areas with both HLA and TCR chains are indistinguishable. Moreover, the spatial conformation of TCR-facing residues can be identical in paired TAA and microbiota-derived epitopes, with exactly the same values of planar as well as dihedral angles.</p> <p><strong>Conclusions:</strong> The data reported in the present study show for the first time the high homology in the linear sequence as well as in structure and conformation between TAAs and peptides derived from microbiota species of the Firmicutes and the Bacteroidetes phyla, which together account for 90% of gut microbiota. Cross-reacting CD8<sup>+</sup> T cell responses are very likely induced. Therefore, the anti-microbiota T cell memory may turn out to be an anti-cancer T cell memory, able to control the growth of cancer developed during the lifetime if the expressed TAA is similar to the microbiota epitope. This may ultimately represent a relevant selective advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.</p>
Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma
ClinicalTrials.gov study NCT03843294. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Immunotherapy Using Precision T Cells Specific to Multiple Common Tumor-Associated Antigen Combined With Transcatheter Arterial Chemoembolization for the Treatment of Advanced Hepatocellular Carcinoma
ClinicalTrials.gov study NCT02638857. IPD Sharing: Not stated. Countries: 1. Publications: 25.
Autologous Dendritic Cells Loaded With Autologous Tumor Associated Antigens for Treatment of Newly Diagnosed Glioblastoma
ClinicalTrials.gov study NCT03400917. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Radical Surgery Followed by Immunotherapy Using Precision T Cells Specific to Multiple Common Tumor-Associated Antigen for the Treatment of Hepatocellular Carcinoma
ClinicalTrials.gov study NCT02632188. IPD Sharing: Not stated. Countries: 1. Publications: 25.
ETAPA I: Peptide-based Tumor Associated Antigen Vaccine in GBM
ClinicalTrials.gov study NCT05283109. IPD Sharing: NO. Countries: 1. Publications: 0.
Identification of breast cancer tumor associated antigens
GEO Series GSE7395. Mus musculus. 15 samples. Type: Expression profiling by array.
The tumor antigen PRAME is a substrate recognition subunit of a Cul2-based ubiquitin ligase and is associated with active NFY promoters
GEO Series GSE26439. Homo sapiens. 5 samples. Type: Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing.
Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy
GEO Series GSE224237. Mus musculus. 9 samples. Type: Expression profiling by high throughput sequencing.
Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma
ClinicalTrials.gov study NCT01456104. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients with High Risk Solid Tumors
ClinicalTrials.gov study NCT05238792. IPD Sharing: NO. Countries: 1. Publications: 0.
Autologous Dendritic Cells Loaded With Autologous Tumor Associated Antigens for Treatment of Advanced Epithelial Ovarian Carcinomas
ClinicalTrials.gov study NCT02033616. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Molecular Analysis of Thrombocytopenia and Cancer (MATAC): Investigating Antigenic Mimicry Between Platelets and Tumor Cells in Patients With Immune Thrombocytopenia (ITP) Associated With Cancer
ClinicalTrials.gov study NCT06444477. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Study of Mana 312 (Multi Tumor-Associated Antigen T Cells) in Adults With AML/MDS After HSCT
ClinicalTrials.gov study NCT04679194. IPD Sharing: NO. Countries: 1. Publications: 0.
Tumor-Associated Antigen-Specific Cytotoxic T-Lymphocytes for Multiple Myeloma
ClinicalTrials.gov study NCT02291848. IPD Sharing: NO. Countries: 1. Publications: 0.
Inhaled mRNA Tumor-associated Antigen Dry Powder Vaccine in Advanced Lung Cancer and Lung Metastasis of Solid Tumors.
ClinicalTrials.gov study NCT06928922. IPD Sharing: Not stated. Countries: 1. Publications: 0.
A Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigens (TAA) Mixed With Montanide ISA-51 VG With Bevacizumab for Patients With Recurrent Glioblastoma
ClinicalTrials.gov study NCT02754362. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Immunotherapy Based on Tumor Associated Antigen-specific Immune Effector Cells
ClinicalTrials.gov study NCT03535246. IPD Sharing: NO. Countries: 1. Publications: 0.
Study of Peptide Vaccination With Tumor Associated Antigens Mixed With Montanide in Patients With CNS Tumors
ClinicalTrials.gov study NCT00935545. IPD Sharing: Not stated. Countries: 1. Publications: 0.
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Allen Brain Atlas
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DANDI Archive for NWB datasets
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International Brain Laboratory public data
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OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.