Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant.
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.
Chen
Qiyuan
Q
Ludwig Institute for Cancer Research, Austin Health, 145-163 Studley Road, Heidelberg, Victoria 3084, Australia.
Jackson
Heather
H
Parente
Phillip
P
Luke
Tina
T
Rizkalla
Mark
M
Tai
Tsin Yee
TY
Zhu
He-Cheng
HC
Mifsud
Nicole A
NA
Dimopoulos
Nektaria
N
Masterman
Kelly-Anne
KA
Hopkins
Wendie
W
Goldie
Heather
H
Maraskovsky
Eugene
E
Green
Simon
S
Miloradovic
Lena
L
McCluskey
James
J
Old
Lloyd J
LJ
Davis
Ian D
ID
Cebon
Jonathan
J
Chen
Weisan
W
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D013737:Testis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D008565:Membrane Proteins; D014614:Vaccines, Synthetic