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 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.