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Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers (NCT03874897). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 108, 3.75 × 108 or 5.0 × 108 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.

So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period. K E Y W O R D S China, clinical trial, new coronavirus pneumonia, new drugs

Background Autophagy, a process for degrading intracellular substances to maintain basal metabolic turnover, is known to be perturbed in gastric cancer. Programmed cell death-1 (PD-1) with its ligand (PD-L1) are important immune checkpoint proteins and their regulation by autophagy has been reported in mouse melanoma and human ovarian cancer. Here, we explored the interplay between autophagy and the PD1/PD-L1 axis in gastric cancer. Methods The expression of PD-L1 in gastric cancer cells was detected by Western blot and flow cytometry analysis. The effect of autophagy inhibition on PD-L1 expression was examined in vitro and in vivo. The molecular mechanisms of the regulation of PD-L1 by autophagy were evaluated in gastric cancer cell lines. The clinical relevance of autophagy-related markers p62/SQSTM1 and LC3 with PD-L1 was evaluated in 137 patients with gastric cancer. Results We found that inhibition of autophagy by pharmacological inhibitors or small interfering RNAs increased the levels of PD-L1 in cultured gastric cancer cells and in xenografts. Interferon (IFN)-γ also promoted PD-L1 gene transcription, whose action was enhanced by autophagy inhibition. Mechanistically, autophagy inhibition led to the accumulation of p62/SQSTM1 and activation of nuclear factor (NF)-κB, in which NF-κB inhibition or p62/SQSTM1 knockdown attenuated PD-L1 induction by autophagy inhibition. Immunohistochemical staining of primary tumor tissues of 137 patients with gastric cancer showed that LC3 and p62/SQSTM1 protein levels were positively correlated with PD-L1 (LC3, p < 0.001; p62/SQSTM1, p < 0.05). The expression of PD-L1 was also positively correlated with tumor lymphocyte infiltration ( p < 0.001). Conclusions We discovered that autophagy regulates PD-L1 expression in gastric cancer through the p62/SQSTM1-NF-κB pathway. Pharmacological modulation of autophagy may thus influence the therapeutic efficacy of PD-L1 blockade in gastric cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1148-5) contains supplementary material, which is available to authorized users.

PURPOSE Effective interventions to improve prognosis in metastatic esophagogastric cancer (EGC) are urgently needed. We assessed the effect of the early integration of interdisciplinary supportive care for patients with metastatic EGC on overall survival (OS). PATIENTS AND METHODS An open-label, phase III, randomized, controlled trial was conducted at Peking University Cancer Hospital & Institute. Patients with previously untreated metastatic EGC were enrolled. Patients were randomly assigned (2:1) to either early interdisciplinary supportive care (ESC) integrated into standard oncologic care or standard care (SC). ESC was provided by a team of GI medical oncologists, oncology nurse specialists, dietitians, and psychologists; patients in the SC group received standard oncologic care alone. The primary end point was OS in the intention-to-treat population. RESULTS Between April 16, 2015, and December 29, 2017, 328 patients were enrolled: 214 in the ESC group and 114 in the SC group. At the data cutoff date of January 26, 2019, 15 (5%) patients were lost to follow-up. The median number of cycles of first-line chemotherapy was five (interquartile range [IQR], 4-7) in the ESC group and four (IQR, 2-6) in the SC group. The median OS was 14.8 months (95% CI, 13.3 to 16.3) in the ESC group and 11.9 months (95% CI, 9.6 to 13.6) in the SC group (hazard ratio, 0.68; 95% CI, 0.51 to 0.9; P = .021). CONCLUSION The early integration of interdisciplinary supportive care is an effective intervention with survival benefits for patients with metastatic EGC. Further optimization and standardization are warranted.