决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Engineered CD147-CAR macrophages for enhanced phagocytosis of cancers.
嵌合抗原受体(CAR)T 细胞疗法在血液系统恶性肿瘤中已显示出有前景的结果,但其在实体瘤中的有效性仍面临挑战。
CAR-T疗法在血液恶性肿瘤中显示前景,但实体瘤应用仍具挑战。肿瘤微环境中的巨噬细胞可吞噬肿瘤细胞,CAR巨噬细胞(CAR-M)因此成为实体瘤治疗的候选方案。CD147是多种癌症中过表达的抗原,靶向CD147的CAR-T和CAR-NK已在肝癌中显示疗效,但此前尚无靶向该分子的CAR-M研究。本研究利用THP-1单核细胞系构建CD147 CAR-M。该细胞具有典型巨噬细胞特征,包括吞噬酵母聚糖颗粒及向M1、M2表型极化的能力。其对K562和MDA-MB-231细胞的抗肿瘤活性增强,且未对正常细胞产生脱靶毒性。研究提示CD147 CAR-M可能成为治疗血液肿瘤和实体瘤的免疫治疗平台。
Chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematologic malignancies, but its effectiveness in solid cancers remains challenging. Macrophages are immune cells residing within the tumor microenvironment. They can phagocytose tumor cells. Recently, CAR macrophages (CAR-M) have been a promising candidate for treating solid cancers. One of the common cancer antigens overexpressed in various types of cancer is CD147. CAR-T and NK cells targeting CD147 antigen have shown significant efficacy against hepatocellular carcinoma. Nevertheless, CAR-M targeting the CD147 molecule has not been investigated. In this study, we generated CAR targeting the CD147 molecule using the THP-1 monocytic cell line (CD147 CAR-M). The CD147 CAR-M exhibited typical macrophage characteristics, including phagocytosis of zymosan bioparticles and polarization ability toward M1 and M2 phenotypes. Furthermore, the CD147 CAR-M demonstrated enhanced anti-tumor activity against K562 and MDA-MB-231 cells without exhibiting off-target cytotoxicity against normal cells. Our research provides valuable insights into the potential of CD147 CAR-M as a promising platform for cancer immunotherapy, with applications in both hematologic malignancies and solid cancers.
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