ABSTRACT
CAR-T cell therapy that targets surface antigens to kill tumor cells specifically has recently become another cornerstone in tumor immunotherapy. In this study, a lentiviral expression plasmid of CAR targeting human epidermal growth factor receptor 2 (HER2) was constructed by genetic engineering. The recombinant plasmid was co-transfected with other packaging plasmids into HEK293T cells by calcium phosphate precipitation to generate lenti-car, which are CAR lentiviral particles. HER2-specific CAR-T cells were obtained by transducing human peripheral blood mononuclear cells with lenti-car. Their specific inhibitory effects on HER2-positive and HER2-negative tumor cells were analyzed in vitro. The constructed CAR-T cells were specifically activated by HER2-expressing tumor cells as indicated by secretion of IFN-γ and IL-2. The inhibitory rate on HER2-positive SK-OV-3 cell line was (58.47±1.72)%, significantly higher than that on the mock-treated control group (P<0.05). The inhibitory rate on HER2-negative K562 cell lines was (11.74±2.37)%, which was not significantly different from that on the control group (P>0.05). Furthermore, when we transfected a HER2-expressing vector into K562, the inhibitory rate increased to (30.41±7.59)%, which was higher than that on HER2-negative K562 (P<0.05). Thus, the constructed second-generation HER2-specific CAR-T cells specifically suppressed growth of tumor cells overexpressing HER2 protein, suggesting that HER2-specific CAR-T cells might prove useful for immunotherapy of HER2-positive cancer.
ABSTRACT
Objective To investigate the possibility of tumor abnormal protein ( TAP) ,as index of diag-nosis and prediction of prognosis in gastrointestinal tumors (GITs).Methods The outpatients and inpatients as well as healthy physical examinees in our hospital were chosen as objects in the present study .The patients were divided into GIT group(120 cases),high-risk GIT group(123 cases)and normal group(117 cases).TAP ex-pression was detected in three groups.These study objects were followed up for one and a half years .Then the re-lationship between TAP expression and the occurrence or recurrence of tumors was analyzed .Rseults There were significant differences(P<0.001)among the three groups on the positive TAP with critical expression rate .TAP detections to GITs diagnosis sensitivity ,specificity ,positive predictive value ,negative predictive value and Youden index were 88.33%,85.83%,75.71%,93.64% and 0.74 respectively.TAP positive non GITs crowd tumori-genesis proportion (23.53%)was significantly higher than that of TAP -negative(0.49%)(P<0.001).GITs TAP positive patients relapse rate(33.33%)was significantly higher than negative ones (6.90%)(P<0.001). Conlcusion TAP can be an index for diagnosis ,early prevention ,monitoring of treatment effect and prediction of prognosis of gastrointestinal tumor .