Our research is geared towards improving vaccine development. Using influenza infection and tumor antigen systems, we are elucidating: the mechanisms associated with immunodominance; the interaction between T cells with different antigen specificity; the interaction between T cells and antigen-presenting cells; methods to enhance cross-presentation of cell associated antigens, and; strategies to enhance memory T cell generation.

In the human system, we have been focusing on the discovery of antigenic epitopes associated with cancer testis antigens, such as NY-ESO-1. Many novel CD4+ and CD8+ epitopes have been identified in melanoma patients either from naturally occurring immune responses, or responses following vaccination with NY-ESO-1 formulated in ISCOMATRIXTM adjuvant. After fully characterizing the most immunodominant T cell responses from these patients, we will systematically investigate the HLA-dependent immunodominance hierarchy of T cell responses in these patients with the aim of developing customized vaccine design based on individual’s HLA typing. We are also investigating the tumor infiltrating T cells (including Treg) of these melanoma patients.

We also have an important role in the LICR's global Cancer Vaccine Program monitoring patient T cell responses to cancer vaccines from several clinical trials that are conducted at the LICR Melbourne-Austin Branch and at multiple international sites.

1. Cebon, J., Knights, A., Ebert, L., Jackson, H., and Chen, W. "Evaluation of cellular immune responses in cancer vaccine recipients: lessons from NY-ESO-1". Expert Rev Vaccines. 9(6): p. 617-29 2010.

2. Hensley, S.E., Zanker, D., Dolan, B.P., David, A., Hickman, H.D., Embry, A.C., Skon, C.N., Grebe, K.M., Griffin, T.A., Chen, W., Bennink, J.R., and Yewdell, J.W., Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses. J Immunol, 2010. 184(8): p. 4115-22.

3. Keech, C.L., Pang, K.C., McCluskey, J., and Chen, W., Direct antigen presentation by DC shapes the functional CD8(+) T-cell repertoire against the nuclear self-antigen La-SSB. Eur J Immunol, 2010. 40(2): p. 330-8.

4. Lev, A., Princiotta, M.F., Zanker, D., Takeda, K., Gibbs, J.S., Kumagai, C., Waffarn, E., Dolan, B.P., Burgevin, A., Van Endert, P., Chen, W., Bennink, J.R., and Yewdell, J.W.. "Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action". Proc Natl Acad Sci U S A. 107(15): p. 6964-9 2010.

5. Ebert, L.M., Liu, Y.C., Clements, C.S., Robson, N.C., Jackson, H.M., Markby, J.L., Dimopoulos, N., Tan, B.S., Luescher, I.F., Davis, I.D., Rossjohn, J., Cebon, J., Purcell, A.W., and Chen, W., A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design. Cancer Res, 2009. 69(3): p. 1046-54.

6. Ebert, L.M., Tan, B.S., Browning, J., Svobodova, S., Russell, S.E., Kirkpatrick, N., Gedye, C., Moss, D., Ng, S.P., MacGregor, D., Davis, I.D., Cebon, J., and Chen, W., The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res, 2008. 68(8): p. 3001-9.

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