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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 Hits847Downloads471 Comment 0

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