Exploring the genetic changes caused by vaccine treatment on MC38 tumor tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE279478 | GEO | 2024/10/20
REPOSITORIES: GEO
Similar Datasets
Project description:Exploring the genetic changes caused by vaccine treatment on MC38 tumor tissue
| PRJNA1173102 | ENA
Project description:The paper describes a model of antitumor vaccine therapy.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
A Mathematical Model of the Enhancement of Tumor Vaccine Efficacy by Immunotherapy
Shelby Wilson and Doron Levy
Bull Math Biol. 2012 July ; 74(7)
Abstract:
TGF-β is an immunoregulatory protein that contributes to inadequate antitumor immune responses in cancer patients. Recent experimental data suggests that TGF-β inhibition alone, provides few clinical benefits, yet it can significantly amplify the anti-tumor immune response when combined with a tumor vaccine. We develop a mathematical model in order to gain insight into the cooperative interaction between anti-TGF-β and vaccine treatments. The mathematical model follows the dynamics of the tumor size, TGF-β concentration, activated cytotoxic effector cells, and regulatory T cells. Using numerical simulations and stability analysis, we study the following scenarios: a control case of no treatment, anti-TGF-β treatment, vaccine treatment, and combined anti-TGF-β vaccine treatments. We show that our model is capable of capturing the observed experimental results, and hence can be potentially used in designing future experiments involving this approach to immunotherapy.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models .
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide.
Please refer to CC0 Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000791 | BioModels
Project description:Purpose:gene discrepancy analysis and signaling pathway of tumor tissues in the PBS, Taraxasterol, DC tumor vaccine and Taraxasterol combined with DC tumor vaccine group
2024-08-01 | GSE245586 | GEO
Project description:Introduction: Optimal approaches to induce T-cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T-cell recruitment, and may be induced by IFNgamma. This study tests the hypothesis that intratumoral administration of IFNgamma will induce CXCL9-11, and will induce T-cell recruitment and anti-tumor immune signatures in melanoma metastases. Patients and Methods: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides (12MP) and received IFNgamma intratumorally. Effects on the tumor microenvironment (TME) were evaluated in sequential tumor biopsies. Adverse events (AE; CTCAE v4) were recorded. T-cell responses to vaccination were assessed in peripheral blood (PBMC) by IFNgamma ELIspot assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression and gene expression. Results: Vaccination and intratumoral administration of IFNgamma were well tolerated. Circulating T-cell responses to vaccine were detected in 6 of 9 patients. IFNgamma increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone nor the addition of IFNgamma promoted immune cell infiltration or induced anti-tumor immune gene signatures. Conclusion: The cancer vaccine did not significantly increase T-cell infiltration of tumors. This study provides intriguing findings highlighting some of the limitations of intratumoral IFNgamma treatment. Although IFNgamma is pivotal in anti-tumor immunity, single intratumoral injection may induce secondary immune regulation that paradoxically limits immune infiltration and effector functions. Therefore, alternate dosing strategies or additional combinatorial treatments may be needed to optimally promote trafficking and retention of T-cells in tumor, which merit further study.
2017-03-01 | GSE79741 | GEO
Project description:To develop a method for improved assessment of the genetic stability of bacterial vaccine strains, we applied next-generation sequencing to a Clostridium tetani model strain (including inter- and intra-lab replicates) and other strains. Data were processed to determine (gain or loss of) gene copy numbers. Strains could easily be distiguished based on gain/loss of prophage-like and CRISPR/Cas genes. We found that the model strain has multiple copies of the plasmid carrying the gene coding for tetanus toxin as well as several other genes. Data were reproducible within and between laboratories. The limit of detection of our method is an order of magnitude better than that of the pulsed-field gel electrophoresis (PFGE) currently used during manufacturing. This approach may part of an approach to reduce animal testing during vaccine manufacturing.
2020-02-15 | GSE144242 | GEO
Project description:Personalized cancer vaccines aim to activate and expand cytotoxic anti-tumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy. To determine the effects of neoantigen-specific CD4+ T cell activation, we generated a new vaccine (PancVAX2) targeting both MHCI- and MHCII-specific neoantigens. Tumor-bearing mice vaccinated with PancVAX2 had significantly improved control of tumor growth and long-term survival benefit without concurrent administration of checkpoint inhibitors. PancVAX2 significantly enhanced priming and recruitment of neoantigen-specific CD8+ T into the tumor with lower PD1 expression after reactivation compared to the CD8+ vaccine alone. Vaccine-induced neoantigen- specific Th1 CD4+ T cells in the tumor were associated with decreased T regulatory cells (Tregs). Consistent with this, PancVAX2 was associated with more pro-immune myeloid-derived suppressor cells and M1-like macrophages in the tumor demonstrating a less immunosuppressive tumor microenvironment. This study demonstrates the biological importance of prioritizing and including CD4 T cell-specific neoantigens for personalized cancer vaccine modalities.
2023-12-11 | GSE244992 | GEO
Project description:Neoantigens are promising immunogens for cancer vaccines and are traditionally delivered as adjuvanted peptide vaccines. Our goal was to understand how an adenoviral vectored neoantigen vaccine would induce tumor immunity compared to a peptide neoantigen vaccine. We generated adenovirus serotype 26 (Ad26) vaccines encoding MC38-specific neoantigens and compared them to an adjuvanted peptide MC38 neoantigen vaccine. The single-shot Ad26 vaccines induced greater neoantigen specific IFN- CD8+ T cell immune responses than the two-shot adjuvanted peptide vaccine in mice, and Ad26.VP22.7Epi also provided superior protective efficacy compared to the peptide vaccine following tumor challenge. Ad26.VP22.7Epi induced a robust immunodominant CD8+ T cell response against the Adpgk neoantigen, while the peptide vaccine induced lower responses against both Adpgk and Reps1 neoantigens. Tumor infiltrating lymphocytes (TILs) from both vaccine groups were analyzed using scRNA-seq and TCR-seq. Vaccinated mice showed increased CD8+ T cell infiltration, with the peptide vaccine inducing more infiltrating CD8+ T cells than the Ad26.VP22.7Epi vaccine. However, Ad26.VP22.7Epi induced CD8+ T cells showed more upregulation of T cell maturation, activation, and Th1 pathways compared to peptide vaccine induced CD8+ T cells, suggesting improved functional T cell quality. TCR-seq of these TILs also demonstrated that Ad26.VP22.7Epi generated larger T cell hyperexpanded clones compared to the peptide vaccine. These results suggest that the Ad26.VP22.7Epi vaccine led to improved tumor control compared with the peptide vaccine due to increased T cell hyperexpansion and functional activation. Our data suggest that future cancer vaccine development strategies should focus on inducing functional hyperexpanded CD8+ T cell responses and not only maximizing tumor infiltrating CD8+ T cell numbers.
2025-02-14 | GSE264579 | GEO
Project description:We used mouse CRC cell line (MC38) to establish a heterotopic mouse model, and applied [89Zr]-labeled PD-L1 antibody KN035 for PET imaging. Attenuated Salmonella typhimurium 3261 was used as an anti-tumor vaccine, and the combined anti-tumor immunotherapy with bivalent genetic vaccine and anti-PD1 antibody Nivolumab was conducted. MicroPET was performed to observe the changes of tumor tissues and expression of PD-L1. We found that the recombinant double-gene plasmids were stably expressed in COS7 cells. Study results showed the combined immunotherapy improved the effectiveness over genetic vaccine alone. This study supports that combination of genetic vaccines and anti-immunocheckpoint immunotherapy can inhibit MC38 tumor growth. Colorectal cancer; Anti-tumor immunotherapy; Genetic vaccine; CEACAM6; 4-1BBL; Anti-PD1 drug.
| S-EPMC9535276 | biostudies-literature
Project description:HPV-associated malignancies continue to present a major health concern despite the development of prophylactic vaccines. Standard therapies offer limited benefit to patients with advanced stage disease. Despite improved outcomes with PD-1 targeted therapies, treatment resistance and modest response rates highlight a significant unmet need to develop novel therapies for these patients. PDS0101 (designated HPV vaccine) is a liposomal nanoparticle HPV16-specific therapeutic vaccine that has been shown to generate strong HPV-specific responses in pre-clinical and clinical studies. Here we assess the efficacy of this HPV vaccine in combination with the tumor-targeting immunocytokine NHS-IL12 (PDS01ADC), plus either aPD-1 or the class I histone deacetylase (HDAC) inhibitor Entinostat. Mice bearing HPV16+, aPD-1 refractory TC-1 and mEER tumors were treated with HPV vaccine, NHS-IL12, and either aPD-1 or Entinostat to determine anti-tumor efficacy and survival benefits. A comprehensive analysis of the tumor microenvironment was performed using flow cytometry, multiplex immunofluorescence, chemokine and cytokine assessment, and scRNAseq with TCR enrichment. Combination of HPV vaccine and NHS-IL12 with either Entinostat or aPD-1 yields significant anti-tumor activity and prolonged survival in aPD-1 refractory models of HPV16+ cancer, with superior activity employing Entinostat versus aPD-1 combination. Entinostat triple therapy increased overall and HPV16-specific tumor CD8+ T cell infiltration with heightened cytotoxicity. TCR sequencing revealed a CD8+ T cell clone unique to vaccine-treated cohorts, which displayed an enriched cytotoxic transcriptional profile with triple therapy. These effects were parallelled by strong differentiation of tumor-associated macrophages (TAMs) towards proinflammatory, anti-tumor M1-like cell states. Single-cell transcriptomic analysis indicated all three agents were required for highest modulation of both CD8+ T cells and TAMs conducive to tumor control. A biomarker signature reflecting the pre-clinical findings was found to be associated with improved survival in patients with HPV-associated malignancies. Together, these findings provide a rationale for the combination of HPV vaccine, NHS-IL12, and Entinostat in the clinical setting for patients with HPV16-associated malignancies.
2025-05-07 | GSE295238 | GEO
Project description:The genetic diversity of JEV vaccine strains SA14-14-2, SA14-5-3 and SA14-2-8 and the WT parental WT strain they were derived from, SA14, were sequenced using Illumina technology. Passages of the strains were also sequenced to observe changes in genetic diversity.
2021-01-21 | E-MTAB-9385 | biostudies-arrayexpress