Dr. Xinping Fu's main projects at the Center for Nuclear Receptors and Cell Signaling are aimed at cancer therapy by developing several novel strategies:

Cancer Virotherapy: We have been developing several oncolytic herpes simplex viruses (HSV) especially for solid tumor treatment with genetic approaches to have them specifically replicated in and kill tumor cells, but not in normal cell and tissues. First, we have utilized tumor specific promoters or MiRNAs to control virus replication in the tumors. Second, we have constructed oncolytic viruses through tumor oncogene pathway- Ras signaling. Third, in order to enhance the potency of virotherapy, we have developed a series of oncolytic HSVs with powerful tumor cell membrane fusion capability. Oncolytic viruses – Fu-10, Synco-2, Synco-2D and Fusion-H2 have shown their potent cell syncytium formation effects in cancer cells from different tissue origins, and provided strong antitumor activities in several tumor models, including breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, without notable toxicity.

Cancer Immunotherapy: Cancer immunotherapy holds promise as a cancer treatment due to its potential to eradicate local or metastatic tumors. Cancer vaccines directly derived from whole tumor cells have a major advantage over those based on identified tumor antigens, in that it includes the entire antigenic repertoire of tumor cells. We have been pursuing our newly developed HSV’s privilege in the development of novel tumor vaccines for cancer treatment and prevention. The first strategy is to use oncolytic viruses such as Synco-2D, FusOn-H2 with powerful cell membrane fusion capability and their potent in situ tumor destruction to develop whole tumor cell vaccination. Our work has shown that destruction of syngeneic murine tumors by those viruses induces effective antitumor immunity that can clear metastatic tumors. Another strategy is to develop targeting autophagy for enhancing tumor antigen presentation. Our lab has developed a special HSV DNA fragment that could produce protein aggregation and lead to autophagic cell death. We utilize this advantage to develop a novel tumor vaccine through autophagic way to enhance tumor antigen presentation. The effectiveness on tumor eradication with this novel method has well been proved in an established murine tumor model.

Cancer Cell Therapy: We modify and convert naïve lymphocytes into tumor-specific killer cells for cancer therapy. Several strategies have been developed for the modification of naïve lymphocytes. First strategy is to replace the natural binding domain of TCR with a single chain antibody that recognizes a tumor-associated antigen. The modified T cells with tumor-specific TCR by gene transduction techniques will attack tumor cells. Secondly, we introduce powerful molecules into T cells to enhance their potency and TCR sensitivity for tumor eradication.

Cancer Stem Cell Study: Strategies of cancer stem cell therapy holds promise for the treatment of drug resistant and refractory tumors. The cancer stem cell, unlike most cancer cells within a tumor, resists chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Cancer stem cell characterization, and their viral and chemotherapy is under way at our lab.