mRNA neoantigen cancer vaccine
COVID-19 mRNA vaccine
Adeno-associated virus (AAV)-based gene therapy
Cancer immunotherapy
Hepatitis B immunotherapy
Translational medicine
Ph.D. Columbia University (Microbiology and Immunology).
Postdoctoral Fellow. Stanford University (Oncology)
Our lab focuses on harnessing the immune system to combat tumors and infectious diseases, aiming for long-term cures for cancer and chronic hepatitis B. We develop cutting-edge technologies, including DNA and mRNA vaccines, adeno-associated viral vector-based gene therapy, small interfering RNA therapies, and advanced animal models. We are currently conducting an Investigational New Drug (IND)-enabling study for a mRNA neoantigen cancer vaccine. As the coordinator of Academia Sinica’s Biotechnology Research Park Translation (BRPT) projects, our team helps researchers in Academia Sinica translate their fundamental discoveries into potential clinical applications.
mRNA Neoantigen Cancer Vaccine Development. While immune checkpoint inhibitors have revolutionized cancer therapy, their limited response rates highlight the need for more targeted approaches. Neoantigen-based cancer vaccines offer a promising solution by enhancing tumor-specific T cell responses, potentially preventing relapse after initial treatments. Following a successful proof-of-concept study demonstrating strong immunogenicity and tumor protection, we are advancing our mRNA neoantigen cancer vaccine to clinical readiness. In collaboration with industry partners, we are progressing through Chemistry, Manufacturing, and Controls (CMC) processes and conducting toxicology, pharmacokinetics, and pharmacodynamics studies. Working closely with clinicians, we are designing a Phase 1 clinical trial and consulting regulatory agencies to finalize our IND application package.
Generation of GPCR Monoclonal Antibodies for Cancer Immunotherapy. META1, a G protein-coupled receptor (GPCR), plays a key role in tumor growth, metastasis, and tumor-associated macrophage-mediated immunosuppression, making it a promising therapeutic target. Developing antibodies against GPCRs is challenging due to their complex membrane structure. We established a novel method to generate monoclonal antibodies (mAbs) targeting GPCRs, using META1 as proof of concept. Our human META1-specific mAbs show no cross-reactivity with mouse META1 and significantly suppress human cancer cell growth in mouse models. We are now characterizing these mAbs to identify candidates for preclinical development.
Curative Immunotherapy for Chronic Hepatitis B. While vaccines prevent hepatitis B virus (HBV) infection, they offer no relief for those already infected, and current antiviral therapies suppress HBV without providing a cure. To address this unmet medical need, we have developed multiple HBV disease models and a cytokine-based immunotherapy that achieves viral clearance in animal studies. Using single-cell RNA sequencing, we are uncovering the cellular and molecular mechanisms underlying this therapy, aiming to translate these findings into clinical solutions for chronic HBV.
The Role of Tumor-Associated Neutrophils in Cancer Immunotherapy. The function of neutrophils within the tumor microenvironment remains controversial, posing a significant challenge in optimizing cancer immunotherapy. Our research has shown that radiation combined with immunotherapy alters neutrophil numbers, phenotypes, and functions within the tumor microenvironment. Using advanced multi-omics technologies, we are uncovering the mechanisms behind these changes. Given that neutrophils are the most abundant immune cells, understanding and manipulating their role could open new avenues for cancer treatment.
Development of Novel AAV Strains for Targeted Gene Therapy. Adeno-associated virus (AAV)-based gene therapies have shown promise with recent drug approvals for various genetic diseases. However, natural AAV strains are effective in only a few human tissues, limiting their broader applications. To address this, we created a chimeric AAV capsid library using SCHEMA-guided protein recombination, comprising over a million variants. Our proof-of-concept study identified novel capsids with over 30- to 100-fold improved transduction in cancer cell lines. We are now screening these capsids in iPSC-derived human cells to enhance gene delivery across diverse tissues, aiming for broader clinical applications.
Bridging Fundamental Research and Early Drug Development. While many groundbreaking therapies originate from academic research, fundamental scientists often lack the knowledge needed to translate discoveries into viable drugs. As CEO of the Translational Medicine Division at the Biomedical Translation Research Center, Dr. Tao has identified key gaps between basic science and drug development. Collaborating with industry experts, we designed streamlined educational modules that provide researchers with essential concepts in translational research, enabling them to advance their innovations without detracting from their primary research focus. This initiative aims to inspire more scientists to bring their discoveries closer to clinical application.
2023 Research Highlights of Academia Sinica
2023 Academia Sinica Outstanding Academic Research Award (中央研究院特優學術研究獎)
2022 Outstanding Biomedical Award, 18th Tien Te Lee Biomedical Awards (第十八屆永信李天德醫藥科技獎)
2003 Outstanding Research Award, National Science Council, Taiwan (國科會傑出研究獎).
2001 ISI Citation Classic Award for “Most-Cited Papers” from 1981-1999 in Taiwan. (ISI台灣經典引文獎).
2000 Outstanding Research Award, National Science Council, Taiwan (國科會傑出研究獎)
1999 Research Award for Junior Research Investigators, Academia Sinica, Taipei, Taiwan (中央研究院年輕學者研究著作獎).
1991 Postdoctoral Fellowship, The Jane Coffin Childs Memorial Fund for Medical Research, USA.
1991 Fellowship in Cancer Research, Stanford University, USA.