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therapeutic interventions

Ongoing research in Dr. He’s laboratory has been focusing mainly on developing effective cancer vaccines and immunotherapy approaches for liver cancer (primarily hepatocellular carcinoma). The incidence of HCC is increasing in the United States, with a high mortality rate due to the lack of effective therapies. Regarding liver cancer vaccine development, Dr. He’s research group has generated a proof-of -principle mouse model showing that antigen engineering by epitope-optimization is a valid approach for creating highly immunogenic cancer vaccines. Published in 2014, this engineered cancer vaccine was found to activate a potent liver cancer antigen (alpha fetoprotein)-specific CD8 response and generate a strong antitumor effect. Currently, in collaboration with Dr. Bjoern Peters at the La Jolla Institute for Allergy and Immunology, Dr. He is using epitope optimization to design liver cancer vaccines that can activate both CD8 and CD4 T cells in an effort to maximally activate liver cancer-specific immune responses. In addition, the He Laboratory is translating this important finding into developing human liver cancer vaccines that can be used to activate human T cells to prevent, or even to treat, human liver cancers. Dr. He’s laboratory is also working to identify T cell clones that can effectively recognize and kill human liver cancer cells. The goal of this research is to identify and clone high quality TCR genes that can be used to engineer human T cells for adoptive cell transfer to treat liver cancer patients. Thus far, Dr. He and his laboratory have identified two HLA-A2-restricted human AFP CD8 epitopes. In collaboration with Dr. Celis, Dr. He’s group is working on developing a prime-boost immunization strategy to effectively induce high levels of activation of hAFP-specific CD8 T cells and then identify and clone those T cells that have the best antitumor effect in an adoptive cell transfer setting. In addition to this translational research, the He Laboratory is also interested in understanding the basic mechanisms of immune activation and in deciphering the parameters that can affect the antitumor efficacy of vaccine-activated immune effector cells. The research led to the discovery of interesting findings that begins to explain why in some cases, high levels of antigen-specific T cells do not correlate with an antitumor effect. This research will promote the design of more effective vaccines that can better correlate with potent antitumor responses. Dr. He’s laboratory also has a continuing interest in understanding the immune suppressive tumor microenvironment and in modulating the inflammation status of the tumor microenvironment to improve the antitumor effect of liver cancer vaccines. In collaboration with Dr. Xue-Feng Bai of Ohio State University, Ebi3 gene-mediated IL27 production was shown to be critical in relieving the immune suppression in the tumor microenvironment (Oncoimmunology. 2015, 4 (7):e989137).