Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells.
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 ΔdalΔdat (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)-γ-producing CD8(+) T cells and IFN-γ secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-10-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.
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yu
Y
Yang
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiajie
J
Hou
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
Zhe
Z
Lin
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Han
H
Zhuo
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Dianyu
D
Chen
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Xudong
X
Zhang
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
Yun
Y
Chen
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Beicheng
B
Sun
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics*; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D047368:Tumor Burden; D014613:Vaccines, Attenuated / Q000235:genetics
D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D004269:DNA, Bacterial; D014613:Vaccines, Attenuated