Journal Article

Immunodominant CD4+Responses Identified in a Patient Vaccinated with Full-Length NY-ESO-1 Formulated with ISCOMATRIX Adjuvant

Hopkins, Wendie, Parente, Phillip, Mifsud, Nicole A., Zhu, He-Cheng, McCluskey, James, Tai, Tsin Yee, Davis, Ian D., Goldie, Heather, Masterman, Kelly-Anne, Jackson, Heather, Cebon, Jonathan, Luke, Tina, Green, Simon, Old, Lloyd J., Rizkalla, Mark, Dimopoulos, Nektaria, Miloradovic, Lena, Chen, Weisan, Chen, Qiyuan, Maraskovsky, Eugene

2004

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Amino Acid Sequence / Antibodies / Antigens / Antigens, Neoplasm - immunology / Biological Sciences / CD4-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - immunology / Cell Line, Tumor / Cell lines / Cells, Cultured / Cultured cells / Dendritic cells / Epitopes / Epitopes - chemistry / Epitopes - immunology / Humans / Identification / Immunology / Lymphocyte Activation / Major Histocompatibility Complex - immunology / Male / Melanoma / Membrane Proteins - immunology / Molecular Sequence Data / Molecules / Peptides / Proteins / T lymphocytes / Testis - immunology / Tumors / Vaccination / Vaccines / Vaccines, Synthetic - immunology