Personalized Breast Cancer Vaccines Based on Genome Sequencing
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ABSTRACT:
PROVIDER: PRJNA801393 | ENA |
REPOSITORIES: ENA
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Project description:Personalized Breast Cancer Vaccines Based on Genome Sequencing
| PRJNA801392 | ENA
Project description:We used a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumour cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. We used MHC-I immunoaffinity purification in a murine colon tumor model from CT26 cells. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software.
2022-04-06 | PXD026463 | Pride
Project description:The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effect of cancer vaccines. Studies have shown that individualized and broad antigens can fully activate anti-tumor immunity and inhibiting the function of TGF-β can facilitate T cell migration to tumor sites. Based on our previous study, we introduced a new vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both individualized and broad antigens, to induce broad antitumor effects and cause immunogenic death. Encouraged by the proinflammatory effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the high affinity between TGF-βR2 and TGF-β, we developed RT-MPs with the SARS-CoV-2 spike protein and TGF-βR2. We found that this spike protein and high TGF-βR2 expression induces the innate immune response and ameliorates the immunosuppressive TME, thereby promoting T cell activation and infiltration, and ultimately inhibiting tumor growth. In addition, when combined with anti-programmed death 1 (anti-PD-1) the engineered RT-MPs were able to generate an immune memory response and eliminate subcutaneous tumors. Our study provides a novel strategy for producing an effective personalized anti-tumor vaccine for clinical application.
2023-10-27 | GSE239631 | GEO
Project description:The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effect of cancer vaccines. Studies have shown that individualized and broad antigens can fully activate anti-tumor immunity and inhibiting the function of TGF-β can facilitate T cell migration to tumor sites. Based on our previous study, we introduced a new vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both individualized and broad antigens, to induce broad antitumor effects and cause immunogenic death. Encouraged by the proinflammatory effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the high affinity between TGF-βR2 and TGF-β, we developed RT-MPs with the SARS-CoV-2 spike protein and TGF-βR2. We found that this spike protein and high TGF-βR2 expression induces the innate immune response and ameliorates the immunosuppressive TME, thereby promoting T cell activation and infiltration, and ultimately inhibiting tumor growth. In addition, when combined with anti-programmed death 1 (anti-PD-1) the engineered RT-MPs were able to generate an immune memory response and eliminate subcutaneous tumors. Our study provides a novel strategy for producing an effective personalized anti-tumor vaccine for clinical application.
2023-10-27 | GSE240108 | GEO
Project description:Personal Neoantigen Cancer Vaccines
| PRJNA401959 | ENA
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:H5N8 influenza virus is a highly pathogenic pathogen for the poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches. In this study, we developed three HA gene-based yeast vaccines and our experimental results demonstrated that all of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided protective efficacy partially due to the high dose of H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccines reshaped the immune cell microenvironment in bursa of Fabriciu to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccines increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidences for further clinical use of these engineered yeast vaccines in poultry.
2023-01-01 | GSE220714 | GEO
Project description:Cance vaccines have become a milestone in immunotherapy, but inadequate activation rate of antigen presenting cells (APCs) and low delivery efficiency of specific antigen have widely limited their clinical application. Here we design an engineered vaccine platform based on targeted delivery of specific antigens to activated APCs. This vaccine platform is implemented by loading stimulator of interferon genes agonist and tumor lysate protein with calcium phosphate as adjuvants, and coating the surface with mannose-modified liposomes. By loading different types of tumor antigen proteins, this nanovaccine platform successfully achieves tumor immunotherapy in breast and colon cancer bearing mice. In addition, personalized nanovaccine prepared from surgically removed tumor lysate proteins also significantly suppresses postsurgical distant tumor. Through the design of nanovaccine platform, we provide an efficient multi-adjuvant delivery platform for multiple types of tumor antigens, and also offer more ideas for personalized vaccine immunization. This nanovaccine platform has great prospects for transformation due to the designability and simplicity for the preparation.
2024-05-14 | GSE267162 | GEO
Project description:Neoantigen-reactive cytotoxic T lymphocytes play a vital role in precise cancer cell elimination. In this study, we demonstrate the effectiveness of personalized neoantigen-based T cell therapy in inducing tumor regression in two patients suffering from heavily-burdened metastatic ovarian cancer. Our approach involved the development of a robust pipeline for ex vivo expansion of neoantigen-reactive T lymphocytes. Neoantigen peptides were designed and synthesized based on the somatic mutations of the tumors and their predicted HLA binding affinities. These peptides were then presented to T lymphocytes through co-culture with neoantigen-loaded dendritic cells for ex vivo expansion. Subsequent to cell therapy, both patients exhibited significant reductions in tumor marker levels and experienced substantial tumor regression. One patient achieved repeated cancer regression through infusions of T cell products generated from newly identified neoantigens. Transcriptomic analyses revealed a remarkable increase in neoantigen-reactive cytotoxic lymphocytes in the peripheral blood of the patients following cell therapy. These cytotoxic T lymphocytes expressed polyclonal T cell receptors (TCR) against neoantigens, along with abundant cytotoxic proteins and pro-inflammatory cytokines. The efficacy of neoantigen targeting was significantly associated with the immunogenicity and TCR polyclonality. Notably, the neoantigen-specific TCR clonotypes persisted in the peripheral blood after cell therapy. Our findings indicate that personalized neoantigen-based T cell therapy triggers cytotoxic lymphocytes expressing polyclonal TCR against ovarian cancer, suggesting its promising potential in cancer immunotherapy.
2023-12-01 | GSE248401 | GEO
Project description:Cancer vaccines utilizing naturally circulating dendritic cell (DC) subsets, such as plasmacutoid DCs (pDCs) and type 2 convential DCs (cDC2s), have demonstrated their potential as a therapy. For melanoma in recent clinical trials. These DC vaccines aim to. human. DC subsets on the. T cell transcriptional program, which. forms the. molecular. basis. of an. antitumor. T cell response, is. poorly understood. In. this study, we investigated the eraly gene expressionsignature of CD8+ T. cells following. stimulation by pDCs or cDC2s. in. a culture system that mimics. the. current protocol of primary DC-based cancer vaccines. Our results demonstrate that pDCs and cDC2s induce a remarkably similar transcriptomic profile in CD8_ T cells, which. is tailored for increased effector function, survival and sensitivity. towards secondary signals. Nonetheless, differences between pDC- and cDC2-induced T cell gene expression signatures encompass genes with a role in proliferation, cytolytic capacity and differentiation. Combining both DC subsets results in a T cell. transcriptomic program that. is very. similar to. the program induced by. pDCs alone. The results suggest that the. choice of DC subsets for use in cancer vaccines impacts the induced antitumor CD8+ T cell response.
2020-04-01 | GSE142631 | GEO