Neng-Yao Shih received his Ph.D. (1996) in molecular and cell biology from the Arizona State University, and followed by a post-doctoral training in the Medical School of Washington University in St. Louis (1997-2000), studying the role of CD2-associated protein in T cell activation. In 2001, he started to develop his scientific career in the National Health Research Institutes, where he is a pioneer on identification of immunogenic tumor-associated antigens (TAAs) from lung cancer patients. In his previous studies, he demonstrated that immune-targeting to those TAAs could significantly provide a better survival benefit on cancer prevention and therapy.
Alpha-Enolase (-ENO; ENO1) is a catalytic enzyme participating in the penultimate step of glycolysis and also poses several non-metabolic functions such as plasminogen-binding. In previous studies, we showed that the statuses of cytosolic and cell-surface ENO1 expression were positively associated with the disease progression and metastatic potential of patients with non-small cell lung cancer (NSCLC) and pancreatic cancers. However, the immune response against ENO1 is reversely correlated with the disease stage of NSCLC patients. Using the ENO1 cancer vaccines in the presence or absence of a novel adjuvant, PELC, to re-build the immune responses, both preventive and therapeutic mouse experiments all showed a remarkable suppression on tumor growth and blockade of lung metastatic colony formation. The anticancer event is merely dependent on an antigen-specific manner. The killing effect is mainly attributed to activation of CD3+CD8+ T lymphocytes, and partially contributed by antibody-mediated cytotoxicity. However, compared to the absence of PELC adjuvant, the presence of PELC in the ENO1 vaccine significantly provided a better therapeutic and survival benefit in any preclinical mouse model. On the other hand, tumor-bearing mice were administrated with monoclonal ENO1 antibody plus activated complements also demonstrated a dramatic tumor suppression and inhibition of tumor metastasis. Collectively, ENO1 can be a potential good and safe target for MHC-I-dependent cancer immunotherapy when using PELC adjuvant. In addition, cell-surface ENO1 may also provide a great opportunity for an effective antibody therapy in the near future.
Bo-Jian Zheng has completed his PhD in 1990 from the University of Hong Kong and postdoctoral studies in 1993 from McMaster University. He is a professor working on Virology and Immunology in Department of Microbiology, the University of Hong Kong. He has published more than 180 peer-reviewed papers in international journals and has been serving as an editorial board member of several journals.
Since March 2013, a novel avian influenza A H7N9 virus has emerged in China and resulted in 458 confirmed infection cases and 177 deaths. The virus contained several human adaptation markers which implied that it might cause outbreaks or even pandemic in the public. The outbreak of this new influenza virus has highlighted the need for the development of universal influenza vaccines. Previously, we have demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of H5N1 virus (H5N1-M2e), could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection of the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20 and 21 between M2e of H5N1 and H7N9, our results showed that H5N1-M2e vaccination with either Freund’s adjuvant or Sigma Adjuvant System (SAS) could still induce high level of anti-M2e antibody, which could cross-react with H7N9-M2e peptide. A mouse adapted H7N9 strain A/Anhui/01/2013m was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggested that the tetrameric H5N1-M2e peptide vaccine could protect different subtypes of influenza virus infections. It thus may be an ideal candidate for universal vaccine development in order to prevent the re-emergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.