IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1.

Prdx2 Upregulation Promotes the Growth and Survival of Gastric Cancer Cells.

Peroxiredoxins (Prdxs) play important roles in cell proliferation, differentiation, and the mediation of intracellular signalling pathways. Prdx2 is an important member of the peroxiredoxin family and is upregulated in many cancers. Until now, the biological functions of Prdx2 in gastric cancer have not been completely understood, and the underlying mechanisms remain elusive. The aim of this study was to identify the role of Prdx2 on the growth of gastric cancer cells and the underlying mechanisms. We demonstrated that Prdx2 was highly expressed in gastric cancer tissues and cell lines and that the over-expression of Prdx2 correlated with the progression of gastric cancer. Further, Prdx2 was silenced with a specific, lentiviral vector-mediated shRNA, and this suppressed the proliferation of gastric cancer cells and promoted the apoptosis of gastric cancer cells. Finally, the knockdown of Prdx2 contributed to the attenuated gastric cancer growth in BALB/c nude mice. In conclusion, these findings demonstrate that Prdx2 may participate in the carcinogenesis and development of gastric cancer.