分类： 生物学 >> 生物医药 提交时间： 2017-03-30
摘要： Lung cancer is one of the leading causes of death with one of the lowest survival rates. However, a subset of lung cancer patients who are of Asian origin and carry somatic mutations in epidermal growth factor receptor or EGFR have responded remarkable well to two tyrosine kinase inhibitors, gefitinib and erlotinib. While EGFR mutation profiles have been reported from Japan, South Korea, and Taiwan, there is no such report from mainland of China where the largest pool of patients reside. In this report, we identified ten somatic mutations from a total of 41 lung cancer patients in China. Among them, seven mutations were found in 17 adenocarcinomas. In contrast to previous reports, eight of these mutations are deletions in exon 19 and two of these deletions are homozygous. These results suggest that a large portion of Chinese adenocarcinoma patients could benefit from gefitinib or erlotinib. This unique mutation profile provides a rationale to develop the next generation of EGFR inhibitors more suitable for the Chinese population.
分类： 生物学 >> 生态学 提交时间： 2017-11-17
Wei, XR [ 1,2,3 ]
Lai, YX [ 1,2,3 ]
Li, J [ 4 ]
Qin, L [ 1,2,3 ]
Xu, YD [ 1,2,3 ]
Zhao, RC [ 1,2,3 ]
Li, BH [ 1,2,3 ]
Lin, SM [ 1,2,3 ]
Wang, SN [ 1,2,3 ]
Wu, QT [ 1,2,3 ]
Liang, QB [ 5 ]
Peng, MY [ 6 ]
Yu, FL [ 6 ]
Li, YQ [ 7 ]
Zhang, XC [ 8 ]
Wu, YL [ 8 ]
Liu, PT [ 9 ]
Pei, DQ [ 1,2 ]
Yao, Y [ 1,2,3 ]
Li, P [ 1,2,3 ]
摘要： In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA-and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cellscould efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA(+)MUC1(+) tumors when combined with MUC1-targeting CAR Tcells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting ofthese antigens could further enhance the antitumor efficacy of CAR T cells.
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