There is limited success in using chimeric antigen receptor (CAR) T cells to treat solid tumors. One of the major reasons is the suppressive tumor microenvironment that impairs the infiltration, expansion and persistence of CART cells in tumor tissues. In this study, we engineered CLDN18.2 specific CART cells to co-express cytokines IL-7 and CCL21 (7×21 CART). Our studies indicated that IL-7 and CCL21 can enhance the survival of CART cells and infiltration of T cells and dendritic cells in tumor tissues. 7×21 CART cells can efficiently destroy different solid tumors with or without preconditioned lymphodepletion chemotherapy and suppress the tumor growth with heterogenous antigen expression in vitro and in vivo. These findings suggest that 7×21 could boost CART cells antitumor activity and may be served as a potential therapy strategy for solid tumors.
BackgroundFecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear.ObjectiveWe conducted this systematic review to assess the efficacy and safety of FMT in UC.Data SourcesPubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes.Data Extraction and SynthesisWe estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies.ResultsTwenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition.ConclusionFMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.
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