AUTHOR=Jia Yan Yan , Tan Wei Jun , Duan Fei Fei , Pan Zhi Ming , Chen Xiang , Yin Yue Lan , Jiao Xin An 

TITLE=A Genetically Modified attenuated Listeria Vaccine Expressing HPV16 E7 Kill Tumor Cells in Direct and Antigen-Specific Manner

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00279

DOI=10.3389/fcimb.2017.00279

ISSN=2235-2988

ABSTRACT=<p>Attenuated <italic>Listeria monocytogenes</italic> (<italic>L. monocytogenes</italic>, LM) induces specific CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses, and has been identified as a promising cancer vaccine vector. Cervical cancer is the third most common cancer in women worldwide, with human papillomavirus (HPV), particularly type 16, being the main etiological factor. The therapeutic HPV vaccines are urgently needed. The E7 protein of HPV is necessary for maintaining malignancy in tumor cells. Here, a genetically modified attenuated LM expressing HPV16 E7 protein was constructed. Intraperitoneal vaccination of LM4Δ<italic>hly</italic>::E7 significantly reduced tumor size and even resulted in complete regression of established tumors in a murine model of cervical cancer. We provided evidence that recombinant LM strains could enter the tumor tissue and induce non-specific tumor cell death, probably via activation of reactive oxygen species and increased intracellular Ca<sup>2+</sup> levels. LM4Δ<italic>hly</italic>::E7 effectively triggered a strong antigen-specific cellular immunity in tumor-bearing mice, and elicited significant infiltration of T cells in the intratumoral milieu. In summary, these data showed LM4Δ<italic>hly</italic>::E7 to be effective in a cervical cancer model and LM4Δ<italic>hly</italic>::E7 induced an antitumor effect by antigen-specific cellular immune responses and direct killing of tumor cells, indicating a potential application against cervical cancer.</p>