B cells enhanced the anti-U251/U373 activity of EphA2-CAR T cells

Chimeric antigen receptor (CAR) T cell therapy is a powerful adoptive immunotherapy against blood cancers, but the therapeutic effect was not efficient enough on solid tumors. B cells have been reported to play a critical role in regulating memory T differentiation and cytotoxic T development. However, as of yet the influence of such B cells on CAR T cells has not been discussed. In this study, using ephrin type-A receptor 2 (EphA2) specific CAR T cells, we cultured B cells successfully to stimulate T cells in vitro, and investigated the cell differentiation and anti-tumor efficiency. We observed that EphA2-CAR T cells stimulated by B cells performed enhanced anti-tumor ability with more interferon γ (IFN γ) production and higher OX40 expression. The differentiation of CAR T cells was arrested after B cells stimulation for more than 7 days with the percentage of central memory T cells (Tcm) increasing. In addition, next generation sequencing was performed. The top expressed genes clustered in activation, leukocyte migration and chemokine signaling pathway contributed to the anti-glioblastoma (GBM) activity of CAR T cells stimulated by B cell. In conclusion, these results indicated the importance of B cells in retarding CAR T cells differentiation and enhancing anti-tumor activity, which paves the way for the rapid exploitation of EphA2-CAR T cells against GBM in the future.