Our laboratory devotes on developing genetically engineerable biologics for cancer therapy, especially immunotherapy. We focus on four types of therapeutic biologics: proteins, virus (gene therapy), bio-nanoparticles, and bacteria. For protein therapy, we employed state-of-the-art techniques, including computational protein design, directed evolution, phage/yeast display, to improve the properties of anti-tumor proteins, such as antibodies/nanobodies, cytokines, CRISPR/Cas proteins, etc. For virus-based gene therapy, we develop novel vehicles by deep engineering of bacteriophage. Bacteriophage has several advantages over the traditional human virus for gene therapy, including cheap production, high yield, and designed tropism to human cells. For bio-nanoparticle therapy, we utilize the outer membrane vesicles (OMVs), which is a highly immunogenic nanoparticle generated by bacteria. OMVs show great tumor-targeting ability and anti-tumor activity, and can be genetically modified by plasmid transformation. For bacterial therapy, several bacteria, including E. coli, can target and colonize in tumors. We exploit bacteria as a live factory for constantly secreting therapeutic payloads into tumor microenvironment.
We have successfully achieved complete remission in murine tumor models using several modalities of our therapies. While continuously improving our drug designs, we will expand our endeavors to more tumor models in mice and potentially other high mammals.
Development of a TNF-α-mediated Trojan Horse for Bacteria-based Cancer TherapyMolecular Therapy, Apr 19, 2022