当前位置:科学网首页 > 小柯机器人 >详情
人类抗PSCA CAR巨噬细胞对胰腺癌具有强大的抗肿瘤活性
作者:小柯机器人 发布时间:2024/4/27 16:07:36

美国希望之城国立医学中心Jianhua Yu等研究人员合作发现,人类抗PSCA CAR巨噬细胞对胰腺癌具有强大的抗肿瘤活性。相关论文于2024年4月24日在线发表于国际学术期刊《细胞—干细胞》。

研究人员开发了针对前列腺干细胞抗原(PSCA)的人类诱导多能干细胞(iPSC)衍生自体嵌合抗原受体(CAR)巨噬细胞(CAR-iMac),它们表达膜结合的白细胞介素(IL)-15和截短的表皮生长因子受体(EGFR),分别用于激活免疫细胞和自杀开关。这些同种异体CAR-iMac在体外和体内对人类胰腺实体瘤表现出很强的抗肿瘤活性,在胰腺癌小鼠模型中减轻了肿瘤负担,提高了生存率。
 
CAR-iMac看起来很安全,没有细胞因子释放综合征或其他体内毒性症状。研究人员优化了CAR-iMac祖细胞的冷冻保存,使其在解冻后仍能保持功能,从而提供了一种现成的同种异体细胞产品,可以开发成CAR-iMac。总之,临床前数据有力地支持了这一人类iPSC衍生平台用于实体瘤(包括胰腺癌)的潜在临床转化。

研究人员表示,由于CAR-T 细胞的局限性,包括 CAR 巨噬细胞在内的细胞免疫疗法替代来源正在出现,用于实体瘤的治疗。人类iPSC为免疫细胞的生成提供了无限的来源。

附:英文原文

Title: Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer

Author: Zahir Shah, Lei Tian, Zhixin Li, Lewei Jin, Jianying Zhang, Zhenlong Li, Tasha Barr, Hejun Tang, Mingye Feng, Michael A. Caligiuri, Jianhua Yu

Issue&Volume: 2024-04-24

Abstract: Due to the limitations of autologous chimeric antigen receptor (CAR)-T cells, alternativesources of cellular immunotherapy, including CAR macrophages, are emerging for solidtumors. Human induced pluripotent stem cells (iPSCs) offer an unlimited source forimmune cell generation. Here, we develop human iPSC-derived CAR macrophages targetingprostate stem cell antigen (PSCA) (CAR-iMacs), which express membrane-bound interleukin(IL)-15 and truncated epidermal growth factor receptor (EGFR) for immune cell activationand a suicide switch, respectively. These allogeneic CAR-iMacs exhibit strong antitumoractivity against human pancreatic solid tumors in vitro and in vivo, leading to reduced tumor burden and improved survival in a pancreatic cancer mousemodel. CAR-iMacs appear safe and do not exhibit signs of cytokine release syndromeor other in vivo toxicities. We optimized the cryopreservation of CAR-iMac progenitors that remainfunctional upon thawing, providing an off-the-shelf, allogeneic cell product thatcan be developed into CAR-iMacs. Overall, our preclinical data strongly support thepotential clinical translation of this human iPSC-derived platform for solid tumors,including pancreatic cancer.

DOI: 10.1016/j.stem.2024.03.018

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00124-3

期刊信息

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