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CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions
Başlık:
CD30-Redirected Chimeric Antigen Receptor T Cells Target Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions
Yazar:
Hong, Lee Kyung, author.
ISBN:
9780438033580
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (143 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Gianpietro Dotti Committee members: Barbara Savoldo; Shehzad Sheikh; Roland Tisch; Yisong Wan; Jason Whitmire.
Özet:
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.
Notlar:
School code: 0153
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(678430.1) | 678430-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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