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- W4246063886 abstract "Abstract Background: Cytokine-induced killer cells which were induced with tumor antigen-pulsed dendritic cells (DC-CIK) immunotherapy is a promising strategy for the treatment of malignant tumors. However, the efficacy was restricted by the immunosuppression of tumor microenvironment mediated by the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) pathway. We, therefore, screened a nanobody which is targeted for CTLA-4 (Nb36), and blocked the CTLA-4 signaling with Nb36 to overcome the negative co-stimulation of effector T cells. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors and used to induce CIK cells in vitro, then co-cultured with DC cells that have received tumor antigens. We tested whether blocking CTLA-4 signaling with Nb36 could promote DC-CIK cells proliferation, pro-inflammatory cytokine production and cytotoxicity in vitro. In vivo experiments, The NOD/SCID mice were injected subcutaneously with HepG2 cells to induce solid tumor. We observe whether this therapy can more effectively inhibit tumor growth in mice. Results: After being stimulated with Nb36, DC-CIK cells presented enhanced proliferation and production of IFN-γ in vitro, thereby strengthening the killing effect on tumor cells. For in vivo experiments, Nb36-treated DC-CIK cells significantly inhibited the growth of subcutaneously transplanted tumors of liver cancer, reduced tumor weight and prolonged the survival of tumor-bearing NOD/SCID mice. Conclusions: These findings demonstrated that in response to CTLA-4 specific nanobody stimulation, DC-CIK cells exhibited superior anti-tumor efficacy. Our findings suggested that DC-CIK cells + Nb36 has potential to treat malignant tumors through in vivo adoptive therapy." @default.
- W4246063886 created "2022-05-12" @default.
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- W4246063886 date "2021-02-17" @default.
- W4246063886 modified "2023-09-27" @default.
- W4246063886 title "A CTLA-4 Blocking Strategy Based on Nanobaby in Dendritic Cell-stimulated Cytokine-induced Killer Cells Enhances Their Anti-tumor Effects" @default.
- W4246063886 doi "https://doi.org/10.21203/rs.3.rs-152575/v1" @default.
- W4246063886 hasPublicationYear "2021" @default.
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