EXTH-33. PRIMING OF SYNNOTCH CAR T CELLS VIA CNS-SPECIFIC ANTIGEN ALLOWS SPATIAL AND TEMPORAL REGULATION OF CAR EXPRESSION, EFFECTIVE HOMING AND PERSISTENCE OF T CELLS IN THE CNS
نویسندگان
چکیده
Abstract One of the key challenges in development CAR-T therapy is absence target antigens that are tumor-specific and have homogenous expression. To safely glioblastoma-associated (GAAs) tumor without attacking normal tissue expressing same GAAs outside brain, we adapted a novel synthetic Notch (synNotch) receptor system established “prime kill” sequential two-receptor CAR circuit. We used glioblastoma- (GBM) specific neoantigen EGFRvIII as priming signal for synNotch reported robust antitumor response mice bearing intracerebral PDX with heterogenous However, less than 20% adult GBM cases express EGFRvIII. Furthermore, expression can diminish over time even after its detection primary GBM, EGFRvIII-synNotch primed T cells may deplete EGFRvIII-expressing via their cytotoxic effects, thereby losing signal. overcome these inherent EGFRvIII-priming strategy, CNS tissue-specific to drive localized against EphA2 IL-13Rα2 bypassed need antigen. found BCAN (also known Brevican) most promising antigen among several CNS-specific cell surface proteins evaluated. When GBM6 received single IV infusion engineered α-BCANsynNotch- > α-EphA2/IL-13Rα2 (B-SYNC) circuit, all (10/10) demonstrated complete regression tumor. B-SYNC were significantly more efficacious constitutively expressed EphA2/IL-13Rα2 cells, associated superior persistence exhausted phenotype. Thus, approach represents conceptual novelty activation. This also enhances translational significance synNotch-CAR by widely extending eligibility EGFRvIII-negative glioma patients. will develop conduct phase I study evaluate our hypothesis.
منابع مشابه
Design and development of CAR-T cells for cancer therapy
Introduction: Today, treatment with CAR-T cells is accepted as an effective treatment for blood malignancies. CAR-T cells are autologous T cells that are engineered by gene transfer techniques to express a chimeric antigen receptor (CAR). Despite the promising results and the approval of six CAR-T cell products; these products have not yet been approved for solid tumors. In addition, the high c...
متن کاملthe clustering and classification data mining techniques in insurance fraud detection:the case of iranian car insurance
با توجه به گسترش روز افزون تقلب در حوزه بیمه به خصوص در بخش بیمه اتومبیل و تبعات منفی آن برای شرکت های بیمه، به کارگیری روش های مناسب و کارآمد به منظور شناسایی و کشف تقلب در این حوزه امری ضروری است. درک الگوی موجود در داده های مربوط به مطالبات گزارش شده گذشته می تواند در کشف واقعی یا غیرواقعی بودن ادعای خسارت، مفید باشد. یکی از متداول ترین و پرکاربردترین راه های کشف الگوی داده ها استفاده از ر...
contribution of setting to the study of characters and the main idea in e. brontes: wuthering heights and t. hardys: return of the native.
this thesis aims to adduce an unmitigated and comprehensive explication concerning the relationship of three significant elements of fiction: setting, chracter and theme. my research is basically placed on two outstanding novels of the 19th century: emily brontes wuthering heights and thomas hardys return of the native. my endeavour lies in studying the correlation among the three above-mention...
15 صفحه اولa tripartite model of efl teachers attributions, burnout, and self-regulation: towards the prospects of effective teaching
همطالعه حاضر به ارائه مدلی برای آموزش موثر زبان انگلیسی می پردازد. مدل حاضر از سه عامل تاثیر گذار در کارایی تدریس معلمان زبان انگلیسی بهره می برد. این سه عامل شامل سبکهای اسنادی، خود تنطیمی و فرسودگی شغلی معلمان ایرانی زبان انگلیسی می باشد. رساله مورد نظر درچهار فاز طراحی شده است: فاز اول شامل طراحی و رواسازی پرسشنامه سبکهای اسنادی معلمان زبان انگلیسی و فاز دوم شامل استفاده از این پرسشنا...
ذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.831