新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 癌症研究 » 【Avery D. Posey】——Driving CAR-T Cells to Glyco-Targets

【Avery D. Posey】——Driving CAR-T Cells to Glyco-Targets

来源:本站原创 2018-08-09 17:46



Avery D. Posey
美国宾夕法尼亚大学  讲师

个人简介:

2016.4—至今
美国宾夕法尼亚大学病理和检验医学系讲师 & Posey 实验室主任
研究领域:糖基化特异性嵌合抗原受体临床转化
1、临床前Anti-Tn-MUC1 (5E5) CAR优化,2018年即将进入一期临床试验
2、研发新的多糖半抗原和多糖抗原表位特异性CAR,治疗神经胶质瘤、膀胱癌和乳腺癌
3、研发体外抗性大幅度提高的突变信号CAR-T细胞
4、利用CAR-T细胞治疗犬类动物白血病,记录抗原逃逸状况,建立人CAR-T细胞治疗模型。

2011.4—2016.3
美国宾夕法尼亚大学 病理和检验医学系博士后
导师:Carl June
研究领域:体内检测、清除肿瘤细胞的CAR的研发和鉴定
1、针对Tn抗原的MUC1设计CAR,使用了5E5 mAb的scFv,并测试了5E5CAR-T细胞针对多个肿瘤靶点在体内&体外的功能。2016年这个CAR将进入临床试验
2、针对SSEA-4设计新的scFv和CAR,并评价了SSEA-4 CAR-T细胞在体内&体外的功能。发现此CAR靶向血管内皮细胞,对机体有害。
3、利用CD2的胞内信号域组建CAR,并与CD-28和CD-137受体比较CD2受体的毒性、信号传递系统和体内持久性。
4、利用CAR进行CD28和ICOS信号域的诱变,并评价这些CAR细胞的信号传递系统、细胞因子分泌、抗肿瘤有效性,还鉴定了作用更好、持续更久的CAR突变。
5、通过创造CAR分子单体,研究CAR聚合动力学,并评价这些单体CAR-T细胞在体外的作用。单体CAR-T细胞在体外表现出了更好的安全性。
6、通过慢病毒转染和RNA电穿孔,研究含4-1BB或CD28共刺激域的CAR-T细胞钙通量、近端&远端信号传递以及不同的基因表达。

演讲题目:Driving CAR-T Cells to Glyco-Targets
演讲摘要:Chimeric antigen receptors are engineered T cell receptors with antibody-driven specificities that have so far been employed to break central tolerance and target self. For instance, redirection of T cells to the pan-B cell marker CD19 has led to dramatic cancer remissions and sustained B cell aplasia inpediatric and adult leukemia patients, with persistence of CAR-T cells demonstrating the best correlation with durable response and remission. Redirection strategies for solid tumors have targeted tumor-associated antigens (TAAs), including Her-2/neu, mesothelin, and CEA, but anti-tumor efficacy has been underwhelming and severe toxicities associated with normal tissue damage have been observed. Most TAAs are often overexpressed in tumors but not exclusive to cancer and CAR T cells with specificity for TAAs can be indiscriminate for normal or malignant tissue. However, cancer-specific glycosylation, particularly the aberrant Tn or sTn O-linked glycans, are found at the plasma membrane in >80% of the most lethal cancers (lung, prostate, breast, colon, ovary, pancreas) and only as glycosylation intermediates within the golgi of normal tissue. These hypoglycosylated cancer glycoantigens decrease cell-cell interactions, increase the mobility and metastatic potential of tumor cells, and associated with poor prognosis. Therefore, safer, cancer-specific CAR-T cells targeting glycosylated antigens are valid approaches for solid tumor therapy. Additionally, the signaling components of CAR-T cells influence the functions of these cells in vitro and in vivo, including cytokine secretion, proliferation, and persistence. We demonstrate that modifications to conventional CAR-T cell signaling can improve anti-tumor efficacy and persistence in solid tumor models. Combined, these results demonstrate a strategy for the development of safe, yet potent cancer-specific immunotherapies for treating most epithelial malignancies.

想了解跟多关于2018(第四届)CAR-T&TCR-T研讨会嘉宾精彩内容吗?我们相约11月,在上海等你来!









版权声明:本文系生物谷原创编译整理,未经本网站授权不得转载和使用。如需获取授权,请点击
温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库