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

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

  • Chen, Q
  • Jackson, H
  • Parente, P
  • Luke, T
  • Rizkalla, M
  • Tai, TY
  • Zhu, H-C
  • Mifsud, NA
  • Dimopoulos, N
  • Masterman, K-A
  • Hopkins, W
  • Goldie, H
  • Maraskovsky, E
  • Green, S
  • Miloradovic, L
  • McCluskey, J
  • Old, LJ
  • Davis, ID
  • Cebon, J
  • Chen, W

publication date

  • June 22, 2004