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CD30-Redirected Chimeric Antigen Rec...

Hong, Lee Kyung.

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CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions./
作者:	Hong, Lee Kyung.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	143 p.
附註:	Source: Dissertations Abstracts International, Volume: 79-12, Section: B.
Contained By:	Dissertations Abstracts International79-12B.
標題:	Medicine. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10747572
ISBN:	9780438033580

CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions.
Hong, Lee Kyung.

CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 143 p.

Source: Dissertations Abstracts International, Volume: 79-12, Section: B.

Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2018.

This item must not be sold to any third party vendors.

Embryonal carcinomas (ECs) and mixed testicular germ cell tumors (TGCTs) containing EC express CD30 and are the most aggressive TGCT subtypes. Chimeric antigen receptor T cells (CAR-Ts) combine the cytotoxic properties of T cells with the antigen specificity of monoclonal antibodies to target antigen-expressing cells, such as infected or cancerous cells. CAR-Ts targeting CD30 (CD30.CAR-Ts) have shown robust anti-tumor activity against Hodgkin's lymphoma, but have not been tested against solid tumors. We tested whether CD30.CAR-Ts could also target ECs using in vitro and in vivo models. CD30.CAR-Ts exhibited anti-tumor activity in vitro against the human EC cell lines Tera-1, Tera-2 and NCCIT, and putative EC stem cells identified by Hoechst dye staining. Cytolytic activity of CD30.CAR-Ts was complemented by sustained proliferation and pro-inflammatory cytokine production. CD30.CAR-Ts also demonstrated anti-tumor activity in an in vivo xenograft NSG mouse model of metastatic EC. Remarkably, we observed that CD30.CAR-Ts, while targeting CD30+ EC tumor cells through the CAR (i.e. antigen-dependent targeting), also eliminated surrounding CD30- EC cells in an antigen-independent manner via cell-cell contact-dependent Fas/FasL interaction. In addition, inducing Fas (CD95) expression in CD30 + but Fas- EC was sufficient to improve CD30.CAR-T anti-tumor activity. Overall, these data suggest that CD30.CAR-Ts can be used as a novel immunotherapy for ECs. Additionally, Fas/FasL interaction between tumor cells and CAR-Ts can be exploited to reduce tumor escape due to heterogeneous antigen expression or to improve CAR-T anti-tumor activity.

ISBN: 9780438033580Subjects--Topical Terms:

641104
Medicine.

CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions.
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520 $a Embryonal carcinomas (ECs) and mixed testicular germ cell tumors (TGCTs) containing EC express CD30 and are the most aggressive TGCT subtypes. Chimeric antigen receptor T cells (CAR-Ts) combine the cytotoxic properties of T cells with the antigen specificity of monoclonal antibodies to target antigen-expressing cells, such as infected or cancerous cells. CAR-Ts targeting CD30 (CD30.CAR-Ts) have shown robust anti-tumor activity against Hodgkin's lymphoma, but have not been tested against solid tumors. We tested whether CD30.CAR-Ts could also target ECs using in vitro and in vivo models. CD30.CAR-Ts exhibited anti-tumor activity in vitro against the human EC cell lines Tera-1, Tera-2 and NCCIT, and putative EC stem cells identified by Hoechst dye staining. Cytolytic activity of CD30.CAR-Ts was complemented by sustained proliferation and pro-inflammatory cytokine production. CD30.CAR-Ts also demonstrated anti-tumor activity in an in vivo xenograft NSG mouse model of metastatic EC. Remarkably, we observed that CD30.CAR-Ts, while targeting CD30+ EC tumor cells through the CAR (i.e. antigen-dependent targeting), also eliminated surrounding CD30- EC cells in an antigen-independent manner via cell-cell contact-dependent Fas/FasL interaction. In addition, inducing Fas (CD95) expression in CD30 + but Fas- EC was sufficient to improve CD30.CAR-T anti-tumor activity. Overall, these data suggest that CD30.CAR-Ts can be used as a novel immunotherapy for ECs. Additionally, Fas/FasL interaction between tumor cells and CAR-Ts can be exploited to reduce tumor escape due to heterogeneous antigen expression or to improve CAR-T anti-tumor activity.
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