Zhirui Wang, DVM, PhD

Wang Laboratory

The Wang Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital uses a unique diphtheria toxin-resistant yeast Pichia Pastoris expression system as a platform to develop novel diphtheria toxin-based recombinant immunotoxins/fusion toxins for specific depletion of targeted cell populations in vivo.

Overview

The Wang Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital is dedicated to developing diphtheria toxin-based recombinant immunotoxins/fusion toxins for cancer immunotherapy, and mechanisms for studying transplantation tolerance and autoimmune diseases.

Group Members

Principal Investigator

Zhirui Wang, DVM, PhD
Head, Wang Laboratory, Center for Transplantation Sciences (CTS)
Assistant Immunologist, Massachusetts General Hospital
Assistant Professor of Surgery, Harvard Medical School

Zhirui Wang, DVM, PhD, completed his doctorate in molecular biology from Justus-Liebig-University of Giessen in Germany in 1995. Dr. Wang completed his Doctor of Veterinary Medicine training in 1982 and his Master of Science in Veterinary Preventive Medicine in 1988 from Shanxi Agricultural University in China. He gained expertise in protein engineering and targeted drug delivery systems through his post-doctoral training in the laboratory of David Neville, MD, at the National Institutes of Health, before joining the Mass General Transplantation Biology Research Center (now known as the Center for Transplantation Sciences) in 2007. Currently, Dr. Wang holds appointments as assistant professor of surgery at Harvard Medical School and assistant immunologist at Mass General.

Research Staff

Zhaohui Wang, DVM
Huiping Zhang
Qi Huang

Research Projects

The Wang Laboratory leads the following research projects:

Diphtheria toxin-based anti-human CCR4 immunotoxin for depleting human CCR4+ cells in vivo: the potential application includes:

  • Directly depleting human CCR4+ tumor cells such as CCR4+ T-cell ALL (acute T lymphoblastic leukemia), CTCL (cutaneous T-cell lymphoma), ATL (adult T-cell leukemia/lymphoma) and PTCL (peripheral T cell lymphoma) 
  • Facilitating cancer treatment and studying the mechanism of transplantation tolerance and autoimmune diseases via specifically depleting CCR4+ Tregs
  • Treatment of the allergic diseases such as asthma via depleting type 2 helper T cells (CCR4+ Th2 cells) and invariant natural killer T cells (CCR4+ iNKT cells). We are collaborating with Soldano Ferrone, MD, and Thomas Spitzer, MD, both of Mass General, to focus on T-cell ALL (acute T lymphoblastic leukemia) as the first target. In addition, we have demonstrated that this CCR4 immunotoxin can cross-species react with non-human primate and swine CCR4+ cells, which will facilitate our preclinical study  

Diphtheria toxin based bivalent human IL-2 fusion toxin (SuperOntak) for depleting human CD25+ cells in vivo: in vitro efficacy characterization demonstrated that the SuperOntak is 100 times more effective than the FDA-approved monovalent human IL-2 fusion toxin, denileukin diffitox (Ontak®). The potential applications include:

  • Directly depleting human CD25+ tumor cells such as human CD25+ CTCL (cutaneous T-cell lymphoma)
  • Cancer immunotherapy and studying the role of Tregs in transplantation tolerance as well as autoimmune diseases via depleting CD25+ Tregs. In collaboration with Celdara Medical, LLC, we are focusing on the preclinical study of CTCL treatment with this SuperOntak. To facilitate the preclinical study, we have also developed both porcine and murine IL-2 fusion toxins

Diphtheria toxin-based immunotoxin/fusion toxins for swine models:

  • Anti-porcine CD3 immunotoxin for depleting porcine CD3 T-cells in vivo
  • Porcine CTLA-4 fusion toxin for depleting porcine CD80+ or CD86+ antigen presenting cells in vivo
  • Porcine CD40L fusion toxin for targeting porcine CD40+ antigen presenting cells in vivo (under investigation)

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