Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Immunotherapy is a promising and highly effective method of targeting hepatocellular carcinoma 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 deliver tumor associated antigens. The study here describes the development and testing of Listeria monocytogenes xprsA2 xhtrA strains as effective vaccine vehicles for the safe delivery of hepatocellular carcinoma antigens. Recombinant listeria monocytogenes xprsA2 xhtrA was engineered to express alpha fetoprotein antigens designed to elicit immunity against hepatocellular carcinoma cells, and tested in a subcutaneous mouse model together with the previously developed listeria monocytogenes xactA prfA* strain. The current results suggest that listeria monocytogenes xprsA2 xhtrA strains represent a highly attenuated yet effective vaccine vector capable of stimulating immunity against hepatocellular carcinoma cells in vivo

Issued also as CD