Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice
説明
<jats:title>Abstract</jats:title><jats:p>Despite the impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR-Ts), the current applications of CAR-T cell therapy are limited by major treatment-related toxicity. Thus, safer yet effective alternative approaches must be developed. In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both <jats:italic>in vitro</jats:italic> and in an aggressive Nalm6 leukemia mouse model. BiTEs were secreted from the transferred T cells and enabled both the transferred and bystander T cells to specifically recognize CD19<jats:sup>+</jats:sup> cell lines, with increased tumor killing ability, prolonged functional persistence, increased cytokine production and potent proliferation compared with the CAR-T cells. More interestingly, in comparison with CD3/CD28 bead-stimulated T cells, T cells that were expanded by a rapid T-cell expansion protocol (REP) showed enhanced anti-tumor activities for both CAR and BiTE RNA-electroporated T cells both <jats:italic>in vitro</jats:italic> and in a Nalm6 mouse model (<jats:italic>P</jats:italic><0.01). Furthermore, the REP T cells with BiTE RNAs showed greater efficacy in the Nalm6 leukemia model compared with REP T cells with CAR RNA (<jats:italic>P</jats:italic><0.05) and resulted in complete leukemia remission.</jats:p>
収録刊行物
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- Blood Cancer Journal
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Blood Cancer Journal 6 (6), e430-e430, 2016-06-03
Springer Science and Business Media LLC
