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1. chinaXiv:201711.02418 [pdf]

PSCA and MUC1 in Non-small-cell Lung Cancer as Targets of Chimeric Antigen Receptor T cells

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 ]
Subjects: Biology >> Ecology

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.

submitted time 2017-11-17 Hits521Downloads337 Comment 0

2. chinaXiv:201703.01011 [pdf]

Identification of EGFR kinase domain mutations among lung cancer patients in China: implication for targeted cancer therapy

Qin, BM; Chen, X; Zhu, JD; Pei, DQ
Subjects: Biology >> Biomedical Laboratory Science

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.

submitted time 2017-03-30 Hits1428Downloads435 Comment 0

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