Mus musculus
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ABSTRACT:
PROVIDER: PRJNA371429 | ENA |
REPOSITORIES: ENA
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Project description:We have shown that DC vaccine is superior to peptide vaccine in terms of priming and expansion of antigen-specific CD8+ T cells. DC vaccine-primed pmel-1 cells displayed better effecter functions than cells by peptide-primed cells in terms of cytokine production and externalization of cytotoxic granules. Furthermore DC vaccine-primed cells were metabolically distinct from peptide-primed cells. To confirm these findings, we performed a microarray analysis using splenic pmel-1 T cells from mice immunized with hgp100 peptide vaccine or DC vaccine. We also used splenic naïve pmel-1 T cells as a control.
2017-08-31 | GSE94538 | GEO
Project description:To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN-γ and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines. To study the fate of melanoma-specific CD8+ T cells after peptide vaccination, we tracked T cell receptor-transgenic pmel-1 T cells in mice vaccinated with heteroclitic gp100_25-33 peptide emulsified in IFA. Splenic pmel-1 CD8+ T cells were purified at 6 and 21 days after vaccination with either gp100/IFA/covax or gp100/saline/covax, and then their total RNA was extracted and used for comparison by gene expression profiling.
2013-03-02 | E-GEOD-43929 | biostudies-arrayexpress
Project description:Recent studies have demonstrated that b-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how b-catenin exerts its functions remains incompletely understood. Here we report that activation of b-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen--human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-b-cateninactive mice exhibited impaired cross-priming and memory re-sponses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Sin-gle cell RNA sequencing (scRNA-seq) analysis revealed that b-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-b-cateninactive mice. Further experiments showed that treating CD11c-b-cateninactive mice with anti-Tim-3 antibody upon anti-DEC-205-hgp100 vac-cination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, sug-gesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. In-deed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth, compared to treatment with DC vaccine alone. Taken together, we have identified the b-catenin/Tim-3 axis as a novel mech-anism to inhibit anti-tumor CD8 T cell immunity, and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy.
2024-05-02 | GSE263715 | GEO
Project description:To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN-γ and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
2013-03-02 | GSE43929 | GEO
Project description:Expression data for naïve IL-2 and IL-12 primed Pmel-1 CD8+ T-cells
| PRJNA128523 | ENA
Project description:Adoptive cell transfer (ACT), an increasingly used immunotherapeutic approach for the treatment of cancer and infectious diseases, typically infuses antigen-specific CD8+ T cells obtained after ex vivo stimulation with patient-derived dendritic cells (DC) loaded with defined peptides. However, broader use of this approach is limited by logistical complexity, variability, cost, and inconsistency in cell quality. To overcome these limitations, we developed a dimeric protein scaffold-based antigen-presentation platform, Immuno-STAT (IST), which delivers peptide-specific TCR activation and costimulatory signaling to robustly expand highly functional antigen-specific CD8+ T cells. We demonstrate that delivering TCR and CD28 signals by IST selectively activates and expands highly functional cytotoxic CD8+ T cells from the naïve CD8+ T cell repertoire specific for the melanoma-associated MART-1 antigen and the HIV-associated SL9 antigen. While naïve MART-1-specific CD8+ T cells were expanded by both MART-1-peptide loaded DC and MART-1-specific IST, naïve SL9-specific CD8+ T cells were expanded only by SL9-specific IST and not by SL9-peptide loaded DC. By enabling ex-vivo expansion of naïve antigen-specific T cells without generation of autologous DC, IST may overcome the practical hurdles limiting the wider use of ACT and expand its use as a therapeutic strategy for both cancer and infectious disease.
2025-07-21 | GSE286286 | GEO
Project description:Adoptive cell transfer (ACT), an increasingly used immunotherapeutic approach for the treatment of cancer and infectious diseases, typically infuses antigen-specific CD8+ T cells obtained after ex vivo stimulation with patient-derived dendritic cells (DC) loaded with defined peptides. However, broader use of this approach is limited by logistical complexity, variability, cost, and inconsistency in cell quality. To overcome these limitations, we developed a dimeric protein scaffold-based antigen-presentation platform, Immuno-STAT (IST), which delivers peptide-specific TCR activation and costimulatory signaling to robustly expand highly functional antigen-specific CD8+ T cells. We demonstrate that delivering TCR and CD28 signals by IST selectively activates and expands highly functional cytotoxic CD8+ T cells from the naïve CD8+ T cell repertoire specific for the melanoma-associated MART-1 antigen and the HIV-associated SL9 antigen. While naïve MART-1-specific CD8+ T cells were expanded by both MART-1-peptide loaded DC and MART-1-specific IST, naïve SL9-specific CD8+ T cells were expanded only by SL9-specific IST and not by SL9-peptide loaded DC. By enabling ex-vivo expansion of naïve antigen-specific T cells without generation of autologous DC, IST may overcome the practical hurdles limiting the wider use of ACT and expand its use as a therapeutic strategy for both cancer and infectious disease.
2025-07-21 | GSE286056 | GEO
Project description:We compared migratory DCs in draining mediastinal lymph node after intranasal administration of different vaccine adjuvants based on CTA1 subunit of cholera toxin. The goal was to determine different characteristics of dendritic cells subsets after pro-inflammatory vs tolerogenic adjuvant. We had 3 groups: CTA1-DD (pro- inflammatory), CTA1(R7K)-DD (tolerogenic) and PBS to define DC which migrate to LN. All vaccine constructs included 3Ea peptide to allow for sorting of DC which took up the vaccine.
2023-05-15 | E-MTAB-12942 | biostudies-arrayexpress
Project description:(1) Murine CD4 T cells: naïve vs peptide treated and naïve vs peptide+LPS treated. (2) Murine CD8 T cells naïve vs HY-specific cells from tolerant mice and naïve vs cells from rejecting mice
| PRJNA136167 | ENA