Construction and assessment of a novel vaccine targeting hepatocellular carcinoma

Abstract

I MMUNOTHERAPY 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.

Nrf2/HO‐1, NF‐κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

“…Moreover, the expression of genes that govern the production of interleukins, enzymes and growth factors is constantly upregulated 15 . This causes a vicious cycle of liver damage and repair that finally results in the disruption of liver processes, chronic inflammation and, ultimately, liver fibrosis 3,16,17 …”

“… 15 This causes a vicious cycle of liver damage and repair that finally results in the disruption of liver processes, chronic inflammation and, ultimately, liver fibrosis. 3 , 16 , 17 …”

“…15 This causes a vicious cycle of liver damage and repair that finally results in the disruption of liver processes, chronic inflammation and, ultimately, liver fibrosis. 3,16,17 If untreated, fibrosis can lead to cirrhosis, hepatic failure and hepatocarcinoma and potentially cause mortality. This process typically takes decades (about 20-30 years), although it can advance quickly, as in the case of biliary atresia, drug-induced liver damage, HIV/HCV coinfection, or HCV infections following liver transplantation.…”