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Immunodominant CD4+ Responses Identified in a Patient Vaccinated with Full-Length NY-ESO-1 Formulated with ISCOMATRIX Adjuvant
Qiyuan Chen, Heather Jackson, Phillip Parente, Tina Luke, Mark Rizkalla, Tsin Yee Tai, He-Cheng Zhu, Nicole A. Mifsud, Nektaria Dimopoulos, Kelly-Anne Masterman, Wendie Hopkins, Heather Goldie, Eugene Maraskovsky, Simon Green, Lena Miloradovic, James McCluskey, Lloyd J. Old, Ian D. Davis, Jonathan Cebon and Weisan Chen
Proceedings of the National Academy of Sciences of the United States of America
Vol. 101, No. 25 (Jun. 22, 2004), pp. 9363-9368
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3372656
Page Count: 6
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There is increasing evidence showing the involvement of CD4+ T cells in initiating and maintaining antitumor immune responses. NY-ESO-1 is expressed by various tumors but not normal tissues except testis. We conducted a cancer clinical trial by using full-length NY-ESO-1 protein formulated with ISCOMATRIX adjuvant and injected into patients intramuscularly. Autologous dendritic cells pulsed with NY-ESO-1 ISCOMATRIX in combination with overlapping synthetic peptides were used to identify immunodominant T cells from a vaccinated patient. We show here the identification and characterization of two novel CD4+ T cell epitopes. T cells specific to these epitopes not only recognized autologous dendritic cells loaded with NY-ESO-1 but also NY-ESO-1-expressing tumor cell lines treated with IFN-γ. One of the two responses identified was greater than the previously identified immunodominant HLA-DPA-restricted response and correlated with NY-ESO-1-specific CD8+ T cell induction after vaccination. This T cell response was vaccinated in most patients who expressed HLA-DR2. This study has systematically surveyed patients vaccinated with full-length tumor antigen for a vaccinated CD4 helper T cell response.
Proceedings of the National Academy of Sciences of the United States of America © 2004 National Academy of Sciences