Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells
Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells作者机构：Liver Transplantation Center The First Affiliated Hospital of Nanjing Medical University Nanjing China and Nanjing Medical University Nanjing China
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2014年第11卷第2期
页 面：184-196页
核心收录：
学科分类：090602[农学-预防兽医学] 08[工学] 09[农学] 0906[农学-兽医学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种]
基 金：supported by grants from the National Natural Science Foundation 国家973计划 the Major Research Plan of the National Natural Science Foundation Natural Science\ Foundation of Jiangsu Province the China Postdoctoral Science Foundation-funded Project the Jiangsu Planned Projects for Postdoctoral Research Funds the Jiangsu Province Laboratory of Pathogen Biology
主 题：cancer stem cell CD24 hepatocellular carcinoma immunotherapy Listeria monocytogenes
摘 要：Attenuated Listeria monocytogenes （LM） is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex （MHC）-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain AdalAdat （Lmdd） to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma （HCC）. After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon （IFN）-7-producing CD8＋ T cells and IFN-7 secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-lO-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1- 6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell （Treg） numbers and an enhancement of specific CD8＋ T-cell activity were observed in the tumor-infiltrating lymphocytes （TILs）. These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.
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