Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance antitumor immunity
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ABSTRACT:
PROVIDER: PRJNA1002297 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25523706_1.fastq.gz | Fastqsanger.gz | |||
| SRR25523706_2.fastq.gz | Fastqsanger.gz | |||
| SRR25523707_1.fastq.gz | Fastqsanger.gz | |||
| SRR25523707_2.fastq.gz | Fastqsanger.gz | |||
| SRR25523708_1.fastq.gz | Fastqsanger.gz |
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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.
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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.
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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 effectiveness of cancer vaccines. Studies show that a personalized and broad antigen repertoire fully activates anti-tumor immunity and that inhibiting the function of transforming growth factor (TGF)-β facilitates T cell migration. In our study, we introduce a vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both personalized and broad antigen repertoire, to induce comprehensive anti-tumor effects. Encouraged by the proinflammatory effects of the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the high affinity between TGF-β receptor 2 (TGFBR2) and TGF-β, we develop RT-MPs with the SARS-CoV-2 spike protein and TGFBR2. This spike protein and high TGFBR2 expression induce the innate immune response and ameliorate the immunosuppressive TME, thereby promoting T cell activation and infiltration and ultimately inhibiting tumor growth. Our study provides a strategy for producing an effective personalized anti-tumor vaccine.
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