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Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention

ABSTRACT: Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention

PROVIDER: PRJNA1167333 | ENA |

REPOSITORIES: ENA

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Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention

Project description:Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in longterm memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. MUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-kB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness.

2024-12-04 | GSE278476 | GEO

Expression of genes in the spleen of WT and MUC1.Tg mice immunized with dendritic cells loaded with MUC1 peptide

Project description:Goal of study: To determine differentially expressed genes with potential roles in tolerance and immunity in MUC1-immunized WT and MUC1.Tg mice WT (C57Bl/6) and MUC1.Tg mice were immunized (i.v.) with dendritic cells loaded with sythetic, human MUC1 peptide. At 24h and 72h splenic RNA from vaccination groups (n=3) was pooled and microarray performed.

2013-01-16 | E-GEOD-43503 | biostudies-arrayexpress

Gene expression data from tumor-bearing mice, either left untreated, treated with MUC1 peptide vaccine, indomethacin, or MUC1 peptide vaccine + indomethacin

Project description:RNA was isolated from the tumors of untreated mice, mice treated with MUC1 vaccine alone, indomethacin alone, or MUC1 vaccine + indomethacin. We used microarrays to identify changes in gene expression between these treatment groups.

2018-01-26 | GSE109643 | GEO

Transcriptomic profiling following de novo hepatitis B vaccination reveals role of granulocytes in non-responders

Project description:As hepatitis B virus is widely spread, WHO recommend vaccination from infancy to reduce acute infection and chronic carriers. However current subunit vaccines are not 100% efficacious and leaves 5-10% persistent non-responders unprotected. To handle large inter-individual variability in immune response after the first Engerix-B vaccination, we employed whole blood early gene expression signatures at day 3 and 7. Immune related pathways are differential expressed in the responders group mostly at day 3 and at day 7 in the non-responders. A notable difference between both groups are significant differential expressed genes at day 0, before vaccination, showing the inter-individual variation. The granulin precursor (GRN) was significant downregulated in responders while upregulated in non-responders. Further absolute granulocytes numbers were significant higher in non-responders. So there is a certain diversity in basic innate immune system.

2019-02-12 | GSE110480 | GEO

Study of the MUC1 Peptide-Poly-ICLC Adjuvant Vaccine in Individuals With Advanced Colorectal Adenoma

Project description:The purpose of this study is to evaluate the immune response to MUC1 - poly-ICLC vaccine, an investigational or study vaccine. The MUC1 - poly-ICLC vaccine is being tested in persons with a history of advanced adenomatous polyps, the precursor to colorectal cancer. The MUC1 - poly-ICLC vaccine is being developed to prevent polyps from advancing into colon cancer and to prevent polyps from recurring. MUC1 is mucus that is normally present on the lining of the human colon. However, MUC1 is expressed in a larger amount and in a modified form on adenomatous polyps and colorectal cancer. These changes in MUC1 are thought to be part of the process of progression from adenomas toward cancer. The goal of a vaccine is to help the immune system in the body identify the changes in MUC1 that accompany the progression to cancer and eliminate the abnormal cells that make abnormal MUC1.

| 2062599 | ecrin-mdr-crc

Gene expression data from tumor-bearing mice, either left untreated, treated with MUC1 peptide vaccine, indomethacin, or MUC1 peptide vaccine + indomethacin

Project description:Gene expression data from tumor-bearing mice, either left untreated, treated with MUC1 peptide vaccine, indomethacin, or MUC1 peptide vaccine + indomethacin

| PRJNA431580 | ENA

Expression of genes in the spleen of WT and MUC1.Tg mice immunized with dendritic cells loaded with MUC1 peptide

Project description:Goal of study: To determine differentially expressed genes with potential roles in tolerance and immunity in MUC1-immunized WT and MUC1.Tg mice

2013-01-16 | GSE43503 | GEO

A223 bintrafusp alfa non-responders and responders

Project description:A223 bintrafusp alfa non-responders and responders

| PRJNA677973 | ENA

Sequencing the anti-MUC1 hybridoma antibody 139H2

Project description:Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at different mucosal surfaces including breast and intestine. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR can be powerful tools because of their multiplicity of binding and possible applications in the diagnosis and treatment of MUC1-expressing cancers. One such antibody is the hybridoma mouse monoclonal 139H2 which is also widely used as a research tool to study non-cancer MUC1. Here we report direct mass spectrometry-based sequencing of hybridoma-derived 139H2 IgG, which enabled reverse engineering of a recombinant 139H2.

2024-03-18 | PXD043489 | Pride

Metabolomics Analysis of Population Genetics (PopGen) for Response to Cholera Vaccination)

Project description:Metabolomics analysis was performed on 112 serum samples that were collected in India at baseline (before Cholera vaccination) and 28 days after Cholera vaccination under the Population Genetics Project (National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) contract HHSN2004000676C). The 112 samples were selected based on titer results which indicated subjects who were either high responders or low responders to the vaccination. 950MHz 1H NMR spectra were acquired for the 112 serum samples.

| ST000008 | MetabolomicsWorkbench

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