Alfred E. Chang, M.D.
Professor, Department of Surgery
Associate Director for Translational Research, Comprehensive Cancer Center
aechang@umich.edu

The main focus of my laboratory is to develop methods to stimulate T cells to respond to tumor antigens. This involves three different areas of investigation:

1) development of tumor vaccines; 2) investigation of in vitro methods to activate tumor-reactive T cells; and 3) investigate the mechanisms of tumor-induced immune suppression that hampers immunotherapy. The laboratory is actively involved in exploring these areas in pre clinical models as well as clinical trials.

In the areas of vaccine development, we have investigated the immunogenicity of several different vaccines that include genetically modified tumor cells expressing immunostimulatory molecules; tumor cells admixed with adjuvants; and tumor-lysate pulsed dendritic cells. The immunogenicity is assessed in animal models where vaccine-primed lymph node cells are evaluated for antitumor reactivity utilizing both in vitro and in vivo assays.

Another focus of the laboratory effort is in the investigation of methods to activate tumor primed T cells that will promote antitumor reactivity as well as proliferative capacity of the T cells. This entails the use of various antibodies known to bind to receptors and/or ligands expresssed by T cells in order to stimulate them. This research effort also involves examination of the role of progressive tumors in suppressing antitumor immunity.

Lastly, the pre-clinical work established in the animal models is being translated into clinical therapy trials. Studies in patients with relapsed cancers being treated with novel vaccine approaches developed in the laboratory as well as adoptive T cell therapy utilizing activation methods are ongoing in the laboratory.

Representative Publications

•  Skitzki J, Craig RA, Okuyama R, Knibbs RN, McDonagh K, Chang AE , Stoolman LM. Donor cell cycling, trafficking and accumulation during adoptive immunotherapy for murine lung metastases. Cancer Res . 64: 2183-2191, 2004.

•  Li Q, Carr AL , Donald EJ, Skitzki JJ, Okuyama R, Stoolman LM, and Chang AE . Synergistic effects of IL-12 and IL-18 in skewing tumor-reactive T-cell responses towards a type 1 pattern. Cancer Res . 65: 1063-1070, 2005

•  Kroon HM, Li Q, Teitz-Tennenbaum S, Whitfield JR, Noone A-M, Chang AE . 4-1 BB costimulation of effector T cells for adoptive immunotherapy of cancer: involvement of Bcl gene family members. J Immunother 2007;30:406-416.

•  Huang J, Wang Y, Guo J, Lu H, Lin X, Ma L, Teitz-Tennenbaum S, Chang AE , Li Q. Radiation-induced apoptosis along with local and systemic cytokine elaboration is associated with DC plus radiotherapy-mediated renal cell tumor regression. Clin Immunology 2007;123:298-310.

•  Wang X, Yuling H, Yanping J, Xinti T, Yaofang Y, Feng Y, Ruijin X, Li W, Lang C, Jingyi L, Zhiqing T, Jingping O, Bing X, Li Q, Chang AE , Sun Z, Youxin J, Jinquan T. CCL19 and CXCL13 Synergistically Regulate Interaction between B Cell Acute Lymphocytic Leukemia CD23+CD5+ B Cells and CD8+ T Cells. J Immunol 2007;179(5):2880-8.