Frontiers in Oncology (Sep 2020)
Co-expressing LRP6 With Anti-CD19 CAR-T Cells for Improved Therapeutic Effect Against B-ALL
Abstract
BackgroundCellular immunotherapies, such as chimeric antigen receptor modified-T cell (CAR-T) therapy, offers excellent potential for tumor treatment. The memory phenotype of CAR-T has been correlated positively with a therapeutic effect on and prognosis of cancer.MethodThe proliferation rates of novel CAR-T was determined by cell counting. The phenotypes of CAR-T cells were then detected by flow cytometry. The cell cytotoxicity against tumor cells in vitro was investigated by lactate dehydrogenase assay and luciferase assay. The cytokines secreted during these assays were determined by the cytometric bead array assay. The antitumor ability in vivo was evaluated in NOG mice.ResultsCo-expression of an LRP6 full-length protein with anti-CD19 CAR significantly improved the memory phenotype of CAR-positive T-cells by enhancing the wnt signaling pathway. As compared with anti-CD19 CAR-T, anti-CD19 CAR-T-LRP6 exhibited more robust cytotoxicity against tumor cells in vitro and in vivo, albeit fewer cytokines were released in vitro. Moreover, the longer survival rate and robust expansion in vivo of anti-CD19 CAR-T-LRP6 cells were found to be effective in inhibiting cancer recurrence.ConclusionsCAR co-expressed with LRP6 could sustain the memory phenotype that enabled permanent relief and may further assist in the development of potent and durable T-cell therapeutics.
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