AUTHOR=He Ping , Tan Zhongqiu , Wei Zhongheng , Wan Cheng-Liang , Yang Shan-Shan 

TITLE=Co-expressing LRP6 With Anti-CD19 CAR-T Cells for Improved Therapeutic Effect Against B-ALL

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01346

DOI=10.3389/fonc.2020.01346

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Cellular 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.</p></sec><sec><title>Method</title><p>The 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 <italic>in vitro</italic> 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 <italic>in vivo</italic> was evaluated in NOG mice.</p></sec><sec><title>Results</title><p>Co-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 <italic>in vitro</italic> and <italic>in vivo</italic>, albeit fewer cytokines were released <italic>in vitro</italic>. Moreover, the longer survival rate and robust expansion <italic>in vivo</italic> of anti-CD19 CAR-T-LRP6 cells were found to be effective in inhibiting cancer recurrence.</p></sec><sec><title>Conclusions</title><p>CAR 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.</p></sec>