Dr. Gang Zeng’s laboratory is currently focused on three research projects. Each has short-, intermediate- and long-term translational potentials, in anticipation of leading to new immunodiagnostics and therapeutics for clinical application.
Project 1: Autoantibody Plus PSA or “A+PSA” technology for prostate cancer diagnosis and risk assessment. Recipient of a NIHR01 grant award.
Zeng’s laboratory is investigating how to integrate autoantibody responses into conventional cancer biomarkers for improved diagnosis and/or prognosis of human cancers. This current line of inquiry will further optimize the “A+PSA” technology with large cohorts of serum samples from prostate cancer patients that are matched to healthy donors by factors including age, sex and ethnic/racial background. Further, Zeng’s lab seeks to validate A+PSA assay in the context of aiding prostate cancer diagnosis in a prospective clinical trial as well as a retrospective risk assessment study. Lastly, this project may have the potential to lead to a Clinical Laboratory Improvement Amendments (CLIA)-certified diagnostic and prognostic assay for prostate cancer.
Project 2: Dendritic cell (DC)-surface receptors for a new class of damage-associated molecular patterns (DAMP). Recipient of the American Cancer Society (ACS) research scholar award.
The processes of how the immune system recognizes pathogens and tissue injuries has been investigated in great detail over the past 15 years. However, it remains poorly understood how the molecular mechanisms govern the initiation of spontaneous immune responses against endogenously arising cancer.
Continuing work his lab began a decade ago, this project hopes to understand cancer and innate immune system interactions, and explain how a cancer/testis antigen NY-ESO-1 induces distinctively strong T cell and antibody responses. Zeng’s team has been investigating intrinsic factors or molecular patterns contributing to the immunogenicity of NY-ESO-1, and found the NY-ESO-1 protein, in vitro, to bind to immature DC, macrophages and monocytes through the cell surface complement C1q receptor and toll-like receptor-4 (TLR4). Further, in vivo, his lab has found the polymeric structure of NY-ESO-1 protein and the host TLR4 status dictate the protein’s immunogenicity, as well as its function as a molecular adjuvant to otherwise weakly immunogenic antigens. Because NY-ESO-1 and other TAA may resemble HMGB-1 in terms of possessing specific DC-surface receptors, they represent a new class of DAMP.
Additional research indicates there is a novel mechanism underlying the adaptive immune responses against endogenously arising human cancers, a finding which may be exploited for novel mechanism-based cancer immunotherapy.
Project 3: Roles of prostate cancer stem cells in castration resistance. Recipient of the Department of Defense (DOD) New Investigator Award.
Zeng’s team is seeking to develop a functional approach to isolating prostate cancers with putative stem cell properties. The expectation is to reveal new roles of prostate cancer stem cells and pluripotency trans-activators in the development of the castration-resistance phenotype.
Selected Cancer-Related Publications:
Liu Y, Zeng G. Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J Immunother. 2012 May;35(4):299-308.
Liu Y, Tian X, Leitner WW, Aldridge ME, Zheng J, Yu Z, Restifo NP, Weiss R, Scheiblhofer S, Xie C, Sun R, Cheng G, Zeng G. Polymeric structure and host Toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo. J Biol Chem. 2011 Oct 28;286(43):37077-84. Epub 2011 Sep 7.
Meng Z, Wang Y, Zhang G, Ke Y, Yan Y, Wu L, Huang Q, Zeng G, Wang Y, Ying H, Jiao S. Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations. J Immunother. 2011 Sep;34(7):525-34.
Xie C, Kim HJ, Haw JG, Kalbasi A, Gardner BK, Li G, Rao J, Chia D, Liong M, Punzalan RR, Marks LS, Pantuck AJ, de la Taille A, Wang G, Mukouyama H, Zeng G. A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases. J Transl Med. 2011 Apr 19;9:43.
Baratelli F, Takedatsu H, Hazra S, Peebles K, Luo J, Kurimoto PS, Zeng G, Batra RK, Sharma S, Dubinett SM, Lee JM. Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in non-small cell lung cancer. J Transl Med. 2008 Jul 22;6:38.