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Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

ABSTRACT: Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficulty in identifying and screening neoantigen-specific T cells limits its widespread application. Here, we prepared neoantigen-reactive T cells (NRTs) after immunization with a tumor lysate-loaded dendritic cell (DC) vaccine (OCDC) for ACT. Our results demonstrated that the OCDC vaccine could induce a neoantigen-specific immune response, and it was feasible to prepare NRTs by loading immunogenic neoantigens onto DCs and coculturing them with spleen lymphocytes from mice immunized with the OCDC vaccine. We then transferred these NRTs back to the LL/2 tumor-bearing mice after OCDC vaccine immunization and found that OCDC vaccine and NRTs adoptive transfer combination treatment could induce a stronger antitumor response. Furthermore, we found that infused NRTs could migrate into the tumor microenvironment to exert antitumor effects. Our research provides a new and convenient method of preparing NRTs for ACT. The clinical translation of this approach has the potential to increase ACT efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE271086 | GEO | 2024/07/05

REPOSITORIES: GEO

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Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

Project description:Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficulty in identifying and screening neoantigen-specific T cells limits its widespread application. Here, we prepared neoantigen-reactive T cells (NRTs) after immunization with a tumor lysate-loaded dendritic cell (DC) vaccine (OCDC) for ACT. Our results demonstrated that the OCDC vaccine could induce a neoantigen-specific immune response, and it was feasible to prepare NRTs by loading immunogenic neoantigens onto DCs and coculturing them with spleen lymphocytes from mice immunized with the OCDC vaccine. We then transferred these NRTs back to the LL/2 tumor-bearing mice after OCDC vaccine immunization and found that OCDC vaccine and NRTs adoptive transfer combination treatment could induce a stronger antitumor response. Furthermore, we found that infused NRTs could migrate into the tumor microenvironment to exert antitumor effects. Our research provides a new and convenient method of preparing NRTs for ACT. The clinical translation of this approach has the potential to increase ACT efficacy.

2024-07-05 | GSE271085 | GEO

Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

Project description:Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scTCR-Seq)

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A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

Project description:There is little insight into or agreement about the signals that control differentiation of memory B cells (MBC) and long-lived plasma cells (LLPC). By performing BrdU pulse-labeling studies, we found that MBC formation preceded the formation of LLPC in an adoptive transfer immunization system, which allowed for a synchronized Ag-specific response with homogeneous Ag-receptor, yet at natural precursor frequencies. We confirmed observations in wild type (WT) mice and extended them with germinal center (GC) disruption experiments and variable region gene sequencing. We thus show that the GC response undergo a temporal switch in its output as it matures, revealing that the reaction engenders both MBC subsets with different immune effector function and, ultimately, LLPC at largely separate points in time. These data demonstrate the kinetics of the formation of the cells that provide stable humoral immunity and therefore have implications for autoimmunity, vaccine development, and for understanding long-term pathogen resistance. Adoptive transfer of B1-8i+/- genetically targeted BALB/cJ mice B cells into AM14 Transgenic (Tg) x VÎº8R genetically targeted BALB/cJ mice. Naive, memory, early and late GC B cells.

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Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

Project description:Personalized dendritic cell vaccine facilitates the preparation of neoantigen-reactive T cells for adoptive transfer (scRNA-Seq)

| PRJNA1129585 | ENA

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