Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant.

Abstract

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-gamma. One of the two responses identified was greater than the previously identified immunodominant HLA-DP4-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.

• Authors: 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, Weisan Chen
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 25 Pg. 9363-8 (Jun 22 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15197261 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Epitopes
• Membrane Proteins
• Vaccines, Synthetic

Topics

• Amino Acid Sequence
• Antigens, Neoplasm (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Line, Tumor
• Cells, Cultured
• Epitopes (chemistry, immunology)
• Humans
• Lymphocyte Activation
• Major Histocompatibility Complex (immunology)
• Male
• Membrane Proteins (immunology)
• Molecular Sequence Data
• Testis (immunology)
• Vaccines, Synthetic (immunology)