气候变化领域集成服务门户(CCPortal): Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown

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DOI	10.1073/pnas.2022830118
	Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown
	Zhang Y.; Xie X.; Yeganeh P.N.; Lee D.-J.; Valle-Garcia D.; Meza-Sosa K.F.; Junqueira C.; Su J.; Luo H.R.; Hide W.; Lieberman J.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	New strategies for cancer immunotherapy are needed since most solid tumors do not respond to current approaches. Here we used epithelial cell adhesion molecule EpCAM (a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells) aptamer-linked small-interfering RNA chimeras (AsiCs) to knock down genes selectively in EpCAM+ tumors with the goal of making cancers more visible to the immune system. Knockdown of genes that function in multiple steps of cancer immunity was evaluated in aggressive triple-negative and HER2+ orthotopic, metastatic, and genetically engineered mouse breast cancer models. Gene targets were chosen whose knockdown was predicted to promote tumor neoantigen expression (Upf2, Parp1, Apex1), phagocytosis, and antigen presentation (Cd47), reduce checkpoint inhibition (Cd274), or cause tumor cell death (Mcl1). Four of the six AsiC (Upf2, Parp1, Cd47, and Mcl1) potently inhibited tumor growth and boosted tumor-infiltrating immune cell functions. AsiC mixtures were more effective than individual AsiC and could synergize with anti-PD-1 checkpoint inhibition. © This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	CD47; Checkpoint blockade; EpCAM aptamer; Gene knockdown; Immunotherapy
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180447
作者单位	Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, United States; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States; Department of Pathology, Harvard Medical School, Boston, MA 02115, United States; Department of Lab Medicine, The Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, United States; The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, 300020, China; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States; Divison of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States; Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Un...
推荐引用方式 GB/T 7714	Zhang Y.,Xie X.,Yeganeh P.N.,et al. Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown[J],2021,118(9).
APA	Zhang Y..,Xie X..,Yeganeh P.N..,Lee D.-J..,Valle-Garcia D..,...&Lieberman J..(2021).Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Zhang Y.,et al."Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).