IP-10 enhances the amplification capacity and antitumor activity of CAR-T cells in vitro and could influence positive outcomes in MM patients treated with CAR-T cell therapy

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has shown impressive outcomes in haematologic malignancies. However, many patients experience a limited response and tumour relapse because of poor expansion and transport. Fourth-generation CARs address some of the limitations of CAR-T cell therapy, and cytokines are frequently included in fourth-generation CARs due to their importance in T cell development and homeostasis. However, new explorations are still needed to provide more desirable possibilities. Here, we first analysed clinical data from 18 patients with multiple myeloma (MM) who received immunotherapy with BCMA-CAR-T cells. The data showed that the basal serum level of IP-10 was correlated with patient outcomes one year after CAR-T cell therapy and that a higher basal serum level of IP-10 was positively associated with progression-free survival (PFS). Next, we performed in vitro experiments using flow cytometry-based assays, enzyme-linked immunosorbent assays, and cytotoxicity assays. The data verified that IP-10 can effectively stimulate the chemotaxis of CD8+ CAR-T cells. In addition, CAR-T cells cultured in IP-10-supplemented medium had a greater proliferation ability and a more powerful ability to kill tumour cells at a lower effector: target ratio. Thus, our findings demonstrate that IP-10 can enhance the function of CAR-T cells, which has important implications for improving CAR-T cell immunotherapy for haematologic malignancies.