Differential gene expression changes to oral immunotherapy by a multi-antigenic peptide at different time points of atherosclerotic disease progression
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PROVIDER: PRJNA434223 | ENA |
REPOSITORIES: ENA
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Project description:To understand the changes in gene expression by oral immunotherapy to a multi-antigenic construct consisting AHC (ApoB, HSP60 and chlamydia pneumonia outer membrane protein) at different stages of atherosclerotic development, double knock out Apobtm2Sgy/Ldltm1Her mice were fed with high-fat after 5 oral doses with respective highfat diet alone controls at 0,6,18 and 30 weeks.
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Project description:We report here that a EMMPRINs-specific cancer peptide vaccination, where the peptide was modified and synthesied as a multiple antigenic peptide (MAP), significantly inhibited tumor growth and metastases. Specifically, we describe changes in the gene expression profile as assessed by RNAseq in tumors derived from mice implanted with the colon tumorigenic carcinoma (CT26 cells), and vaccinated with either a control scrambled multiple antigenic peptide (Scr-MAP) or with an epitope-specific EMMPRIN multiple antigenic peptide (designated 161-MAP).
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Project description:CD4 T cell responses are characterized based on a limited number of molecular markers selected from exisiting knowledge. The goal of the experiment was to assess antigenic-peptide specific T-cell responses in vitro without bias using microarrays. PBMCs were isolated from 2 donors with allergy. The cells were stimulated with antigenic peptides derived from silver birch wood and cat for 24 hours. Unstimulated cells were cultured without the peptides for 24 hours.
2016-08-15 | E-GEOD-72373 | biostudies-arrayexpress
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2016-08-15 | GSE72373 | GEO
Project description:Recent studies revealed that treatment resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptide derived from tumor-associated antigens (TAAs), thus identification of tumor-associated antigens (TAAs) expressed in CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires large scale of sample and it is challenging for CSCs/CICs. In this study, we established novel bladder CSC/CIC model from a bladder cancer cell line UM-UC-3 cells using ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH) high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immune deficient mouse. HLA ligandome analysis and gene expression (CAGE) using ALDHhigh clone cells revealed distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we identified GRIK2 derived antigenic peptide is specifically expressed in CSCs/CICs. GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressed UM-UC-3 cells and ALDHhigh clone cells indicating that GRIK2 peptide can be a novel target for bladder CSCs/CICs-targeting immunotherapy.
2021-10-01 | GSE166947 | GEO
Project description:Peptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
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Project description:Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8+ T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell–based immunotherapy of MM.
2022-07-19 | PXD035324 | Pride
Project description:In recent years the clinical success of T cell-based immunotherapy approaches has revolutionized treatment of solid tumors and hematological malignancies. However, still some patients do not respond to available therapies at all, others for limited time only. A promising low side-effect approach is peptide-based immunotherapy, which relies on specific immune recognition of tumor-associated human leucocyte antigen (HLA)-presented peptides. In this study, we developed a workflow for the immunopeptidome-guided design of off-the shelf warehouses for personalized peptide vaccines using the example of chronic lymphocyte leukemia (CLL). The so defined warehouses could provide the basis for different T cell-based immunotherapy approaches such as TCR-engineered T cell transfer or multi-peptide vaccinations. The warehouse approach enables a fast and cost-effective way to provide a personalized T cell-based immunotherapeutic approach. The here defined peptide warehouse is already utilized for a personalized multi-peptide vaccine trial (iVAC-XS15-CLL01, NCT04688385).
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Project description:Drug-tolerant cancer persister cells were reported fifteen years ago as cells in a quiescent, reversible cell state which tolerates unattenuated cytotoxic drug stress. It remains unknown whether a similar phenomenon contributes to immune evasion. Here we report an antigenic persister state which survives weeks of cytotoxic T lymphocyte (CTL) attack. In contrast to immune evasion mechanisms that limit immune detection or activation, antigenic persisters robustly activate CTLs which deliver Granzyme B, secrete IFNγ, induce tryptophan starvation, and initiate persister cell apoptosis. However, instead of dying, persisters paradoxically leverage apoptotic stress to suppress inflammatory death and acquire mutations and epigenetic changes which enable outgrowth of CTL-resistant cells. Furthermore, persister cells undergoing sublethal apoptosis are enriched in inflamed human and mouse tumors which have regressed during immunotherapy. These findings reveal that adaptive evolution mediated by persister cells surviving direct T cell attack presents a barrier to complete immune-mediated tumor rejection.
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Project description:Low-grade gliomas (LGGs) are the most common brain tumor of childhood. Children with LGGs are ideal candidates for immunotherapy due to slow tumor growth, and as these children are otherwise healthy, and often have intact immune systems. We recently reported in an early phase clinical trial that vaccine treatment elicited strong biologic responses in LGG patients, compared with our experience in adult and pediatric high-grade brain-stem and non-brain stem gliomas. Additionally, we observed radiographic responses of stable disease (n=7), partial response (n=3), and complete response (n=2) following therapy. These remarkable results prompted us to initiate a phase II trial utilizing this strategy in pediatric LGGs. In order to identify potential peripheral response patterns in each response group, we performed Illumina RNA-sequencing on PBMCs samples (n=54), collected either prior to treatment or at multiple time points following treatment.
2018-04-03 | E-MTAB-6270 | biostudies-arrayexpress