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