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

• DOI: 10.1073/pnas.0403271101
• Publication Date: 2004-06-15T18:30:48Z
• 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
• Keywords: CD4-Positive T-Lymphocytes; Male; Vaccines, Synthetic; Molecular Sequence Data; Membrane Proteins; CD8-Positive T-Lymphocytes; Lymphocyte Activation; CD4+ T cells; 3. Good health; Major Histocompatibility Complex; Epitopes; 03 medical and health sciences; 0302 clinical medicine; Antigens, Neoplasm; Cell Line, Tumor; Testis; Humans; Amino Acid Sequence; Tumor antigen; Vaccine; Cells, Cultured

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.