Immunodominant CD4 + responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant
| Autor: | Mark Rizkalla, Ian D. Davis, Heather Goldie, He-cheng Zhu, Simon Green, Phillip Parente, Lena Miloradovic, Lloyd J. Old, Wendie Hopkins, Nicole A. Mifsud, Nektaria Dimopoulos, Kelly-Anne Masterman, Weisan Chen, Jonathan Cebon, Tina Luke, Eugene Maraskovsky, Qiyuan Chen, James McCluskey, Heather Jackson, Tsin Yee Tai |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male T cell Molecular Sequence Data CD8-Positive T-Lymphocytes Lymphocyte Activation Major histocompatibility complex Epitope Major Histocompatibility Complex Epitopes Immune system Antigen Antigens Neoplasm Cell Line Tumor Testis medicine Humans Amino Acid Sequence Cells Cultured Vaccines Synthetic Multidisciplinary CD40 biology Membrane Proteins Biological Sciences Virology Tumor antigen medicine.anatomical_structure Immunology biology.protein CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:9363-9368 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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-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. |
| Databáze: | OpenAIRE |
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