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 Centre and at multiple international sites.

1. 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, 69(3): p. 1046-54 2009.

2. 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, 68(8): p. 3001-9 2008.

3. Lev, A., Takeda, K., Zanker, D., Maynard, J.C., Dimberu, P., Waffarn, E., Gibbs, J., Netzer, N., Princiotta, M.F., Neckers, L., Picard, D., Nicchitta, C.V., Chen, W., Reiter, Y., Bennink, J.R., and Yewdell, J.W., The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation. Immunity, 28(6): p. 787-98 2008.

4. Chen, W. and Mccluskey, J., Immunodominance and immunodomination: critical factors in developing effective CD8+ T-cell-based cancer vaccines. Adv Cancer Res, 95: p. 203-47 2006.

5. Jackson, H., Dimopoulos, N., Mifsud, N.A., Tai, T.Y., Chen, Q., Svobodova, S., Browning, J., Luescher, I., Stockert, L., Old, L.J., Davis, I.D., Cebon, J., and Chen, W., Striking immunodominance hierarchy of naturally occurring CD8+ and CD4+ T cell responses to tumor antigen NY-ESO-1. J Immunol, 176(10): p. 5908-17 2006.

6. Pang, K.C., Sanders, M.T., Monaco, J.J., Doherty, P.C., Turner, S.J., and Chen, W., Immunoproteasome subunit deficiencies impact differentially on two immunodominant influenza virus-specific CD8+ T cell responses. J Immunol, 177(11): p. 7680-8 2006.

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