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:Cancer peptide vaccines hold promise as therapeutic approach, but their effectiveness has been hampered by lack of suitable antigens and the variability of HLA backgrounds among patients, which restricts their applicability.. We here introduce a novel warehouse concept for the construction of personalized peptide vaccines and outline its successful implementation in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 20 CLL patients, in at least partial remission (PR) after treatment with Bruton’s tyrosine kinase inhibitors, were vaccinated with a personalized vaccine selected from a premanufactured immunopeptidome-defined CLL-associated peptide warehouse. Primary objective was immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was feasible throughout, confirming the success of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions the most common adverse events. Almost all patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses after immune-chemotherapy and the lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the here proven immunopeptidome-guided warehouse-based vaccine design with a strong novel adjuvant to evaluate personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies.
2026-01-22 | PXD059004 | Pride
Project description:Engineering irradiated tumor-derivedmicroparticles as personalized vaccines toenhance antitumor immunity
| PRJNA1000457 | ENA
Project description:Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance antitumor immunity
| PRJNA1002297 | ENA
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:Human iPSC-based personalized cell therapy of PD
| PRJNA1118835 | ENA
Project description:Human iPSC-based personalized cell therapy of PD
| PRJNA1118836 | ENA
Project description:Personalized mRNA neoantigen vaccines demonstrate great potential in cancer therapy, but their customization typically requires more than three months, risking the loss of the optimal therapeutic window for patients. This delay is primarily due to the reliance of current mRNA vaccine production on plasmid fermentation and in vitro transcription (IVT), which involve multiple complex steps. Chemically synthesized RNA oligonucleotides, such as antisense oligonucleotides (ASOs), are produced sparing DNA templates or IVT, thus enabling rapid manufacturing. However, ASOs are limited in length, which precludes their ability to encode proteins. Here, we introduced a 39 nucleotides cap-independent translation enhancer (CITE) element termed BBV that can drive RNA translation. Furthermore, BBV was compatible with efficient rolling circle translation (RCT). We chemically synthesized RNA oligonucleotides containing BBV and gene of interest (GOI) with characteristic 5’-OH and 3’-P termini, which could undergo circularization by endogenous RtcB RNA ligases and efficiently encode proteins through RCT in mammalian cells. We designated these RNA oligonucleotides as Protein-Encoding RNA Oligonucleotides (PEOs). Notably, compared with IVT-produced RNAs, PEOs contained undetectable levels of proinflammatory double-stranded RNAs and exhibited minimal immunogenicity. We further demonstrated that PEO-OVA (encoding OVA antigens) significantly inhibited tumor growth comparable to mRNA vaccine. In an orthotopic glioma model, PEO vaccine also exhibited therapeutic benefits with checkpoint blockade therapy. This study establishes an IVT-free RNA vaccine platform that enables rapid, safe, and highly druggable manufacturing of personalized cancer vaccines, offering substantial potential for clinical application.
2026-07-03 | GSE305709 | 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