小柯机器人

切换到桌面版
科学家研发出靶向CD133的胶质母细胞瘤免疫疗法
2020-05-30 13:47
来源：小柯机器人

加拿大麦克马斯特大学Sheila Singh、Jason Moffat等研究人员合作研发了靶向CD133的胶质母细胞瘤免疫疗法。2020年5月27日，《细胞—干细胞》在线发表了这一成果。

据研究人员介绍，CD133在多种实体瘤中标记自我更新的癌症干细胞（CSC），而CD133+肿瘤起始细胞是多种侵袭性癌症（包括胶质母细胞瘤GBM）中化学耐药和放射耐药的已知标志物，可能会导致肿瘤异质性。
 
研究人员报道了三种基于人类抗CD133抗体片段的免疫治疗方法，这些抗体片段靶向糖基化和非糖基化CD133中存在的独特表位，并研究了它们在GBM患者衍生模型中对CD133+细胞的靶向作用。研究人员生成了免疫球蛋白G（IgG）（RW03-IgG）、双重抗原T细胞衔接蛋白（DATE）和CD133特异性嵌合抗原受体T细胞（CAR-T）：CART133。
 
这三者均表现出靶向患者来源CD133+GBM细胞的活性，而CART133细胞在患者来源的GBM异种移植模型中显示出优异的功效，但不会对人源化CD34+小鼠的正常CD133+造血干细胞产生不利影响。因此，CART133细胞可能是靶向人类GBM或其他抗药性原发癌中CD133+ CSC的治疗策略。
 
附：英文原文

Title: The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma

Author: Parvez Vora, Chitra Venugopal, Sabra Khalid Salim, Nazanin Tatari, David Bakhshinyan, Mohini Singh, Mathieu Seyfrid, Deepak Upreti, Stefan Rentas, Nicholas Wong, Rashida Williams, Maleeha Ahmad Qazi, Chirayu Chokshi, Avrilynn Ding, Minomi Subapanditha, Neil Savage, Sujeivan Mahendram, Emily Ford, Ashley Ann Adile, Dillon McKenna, Nicole McFarlane, Vince Huynh, Ryan Gavin Wylie, James Pan, Jonathan Bramson, Kristin Hope, Jason Moffat, Sheila Singh

Issue&Volume: 2020-05-27

Abstract: CD133 marks self-renewing cancer stem cells (CSCs) in a variety of solid tumors, andCD133+ tumor-initiating cells are known markers of chemo- and radio-resistance inmultiple aggressive cancers, including glioblastoma (GBM), that may drive intra-tumoralheterogeneity. Here, we report three immunotherapeutic modalities based on a humananti-CD133 antibody fragment that targets a unique epitope present in glycosylatedand non-glycosylated CD133 and studied their effects on targeting CD133+ cells inpatient-derived models of GBM. We generated an immunoglobulin G (IgG) (RW03-IgG),a dual-antigen T cell engager (DATE), and a CD133-specific chimeric antigen receptorT cell (CAR-T): CART133. All three showed activity against patient-derived CD133+GBM cells, and CART133 cells demonstrated superior efficacy in patient-derived GBMxenograft models without causing adverse effects on normal CD133+ hematopoietic stemcells in humanized CD34+ mice. Thus, CART133 cells may be a therapeutically tractablestrategy to target CD133+ CSCs in human GBM or other treatment-resistant primary cancers.

DOI: 10.1016/j.stem.2020.04.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30147-8

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章：《细胞—干细胞》：Online/在线发表

分享到:

0