Construction and assessment of a novel vaccine targeting hepatocellular carcinoma

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© 2020 National Information and Documentation Center (NIDOC). IMMUNOTHERAPY is a promising and highly effective method of targeting hepatocellular carcinoma (HCC) cells and improving patient outcomes. There is a continuing need for the development and refinement of current vaccine vehicles to safely target tumors while stimulating robust cell-mediated immune responses. The facultative intracellular bacterium Listeria monocytogenes has proven to be an effective vehicle for the design of cancer vaccines that stimulate potent and long CD8+ T-cell responses. Critical facets of its effectiveness relate to the ability of gaining access to the cytosol of infected host cells and delivering tumor-associated antigens. Here we describe the development and testing of L. monocytogenes ΔprsA2 ΔhtrA strains as effective vaccine vehicles for the safe delivery of HCC antigens. Recombinant L. monocytogenes ΔprsA2 ΔhtrA was engineered to express α-fetoprotein antigens designed to elicit immunity against HCC cells, and tested in a subcutaneous mouse model together with the previously developed L. monocytogenes ΔactA prfA*strain. The results suggest that L. monocytogenes ΔprsA2 ΔhtrA strains may represent a highly attenuated yet effective vaccine vector capable of stimulating immunity against HCC cells in vivo.

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