Bin Zhang

Bin Zhang, MD,PhD
Associate Professor
Department of Medicine - Division of Hematology/Oncology

Cancer immunotherapy by endogenous or adoptively transferred antitumor T cells


Research cluster: Cancer Biology

E-mail:   bin.zhang@northwestern.edu

Cancer immunotherapy by endogenous or adoptively transferred antitumor T cells is complementary to conventional therapies, including surgery, radiotherapy, or chemotherapy. However, a number of obstacles hinder the generation of effective antitumor T-cell immunity. During tumor progression, tumor cells foster a tolerant microenvironment and activate a plethora of immunosuppressive mechanisms, which may act in concert to counter effective immune responses. My laboratory is focused primarily on effector and regulatory molecules controlling cancer specific T lymphocytes before and during immunotherapy, especially studying a negative immunoregulatory mechanism used for immune evasion in the tumor microenvironment. The overall goal is to develop novel and feasible strategies to improve cancer immunotherapy.

We have demonstrated that targeting the tumor stroma for destruction by adoptively transferred T cells becomes a new and important focus for successful immunotherapy of established tumors (JEM 2007, Can Res. 2008, JCI 2008).  Furthermore, this work represented an important new paradigm of bystander killing due to cross-presentation which can occur during the effector phase of an immune response. 

Evading immune destruction has recently emerged as one of the “hallmarks of cancer.” The identification of multiple mechanisms of tumor-induced immune evasion provides an array of novel targets for new cancer therapies. We have recently reported a tumor-intrinsic immunosuppressive mechanism whereby tumor an host CD73 functions as an ecto-enzyme to produce extracellular adenosine which limits anti-tumor T cell immunity to promote tumor growth via adenosine receptor signaling (Can Res. 2010, JCI 2011). Given the well-established immune effects of CD39/CD73 and the A2A adenosine receptor (A2AR) on cancer growth and metastasis, the phosphohydrolysis of extracellular ATP to adenosine can now be viewed as one of the most important immunosuppressive regulatory pathways in the tumor microenvironment. We are further exploring the detailed mechanisms of CD73 by which the tumors evade the immune system using a combination of molecular, biochemical, and mouse genetic approaches, and to accomplish the targeted elimination of CD73 as a novel means to enhance cancer immunotherapy. Moreover, to determine the translational relevance of targeted CD73 cancer therapy, we are developing the new anti-human/mouse CD73 monoclonal antibodies that will be tested in the established pre-clinical tumor models in the near future.
Other ongoing projects include the discovery of antigenic determinants expressed in tumor cells or stromal cells as novel targets; and the development of new animal models that can be employed in preclinical studies to most reflect human clinical trials.

Selected Publications:

Zhang B*, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A, Yu P, Fu YX, Weichselbaum RR, Rowley DA, Kranz DM, Schreiber H. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. Journal of Experimental Medicine 2007; 204: 49-55 (Research Highlight: Nature Reviews Immunology 2007; 7:89) (* co-corresponding author) 

Zhang B*, Zhang Y, Bowerman NA, Schietinger A, Fu YX, Kranz DM, Rowley DA, Schreiber H. Equilibrium between host and cancer caused by effector T cells killing tumor stroma. Cancer Research 2008; 68:1563-71 (Cover Feature Article; reported in BioWorldÒ Today 2008;19(46)1-7;  highlighted in Future Oncol. (2008);4(2)) (* corresponding author) 

Zhang B*, Karrison T, Rowley DA, Schreiber H. IFN-g and TNF-dependent bystander eradication of antigen loss variants in established cancers. Journal of Clinical Investigation 2008; 118:1398-1404 (Highlighted in SciBX) (* corresponding author) 

Jin D, Fan J, Wang L, Thomson LF, Liu A, Daniel BJ, Shin T, Curiel TJ, Zhang B. CD73 on tumor cells impairs anti-tumor T cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Research 2010; 70:2245-55 (Cover Sidebar Feature)

Wang L, Fan J, Thomson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. Journal of Clinical Investigation 2011;121:2371-82.

Zhang B. Targeting the stroma by T cells to limit tumor growth. Cancer Research 2008; 68:9570-3

Zhang B. CD73: A novel target for cancer immunotherapy. Cancer Research 2010;70:6407-11

Zhang B. CD73 promotes tumor growth and metastasis. OncoImmunology 2012; 1:67-70

Zhang B. Opportunities and challenges for anti-CD73 cancer therapy. Immunotherapy 2012, in press


Pubmed

View Publications by Bin Zhang listed in the National Library of Medicine (PubMed).