NY-ESO-1 protein formulated in ISCOMATRIX adjuvant is a potent anticancer vaccine inducing both humoral and CD8+ t-cell-mediated immunity and protection against NY-ESO-1+ tumors.
NY-ESO-1 is a 180 amino-acid human tumor antigen expressed by many different tumor types and belongs to the family of "cancer-testis" antigens. In humans, NY-ESO-1 is one of the most immunogenic tumor antigens and NY-ESO-1 peptides have been shown to induce NY-ESO-1-specific CD8(+) CTLs capable of altering the natural course of NY-ESO-1-expressing tumors in cancer patients. Here we describe the preclinical immunogenicity and efficacy of NY-ESO-1 protein formulated with the ISCOMATRIX adjuvant (NY-ESO-1 vaccine). In vitro, the NY-ESO-1 vaccine was readily taken up by human monocyte-derived dendritic cells, and on maturation, these human monocyte-derived dendritic cells efficiently cross-presented HLA-A2-restricted epitopes to NY-ESO-1-specific CD8(+) T cells. In addition, epitopes of NY-ESO-1 protein were also presented on MHC class II molecules to NY-ESO-1-specific CD4(+) T cells. The NY-ESO-1 vaccine induced strong NY-ESO-1-specific IFN-gamma and IgG2a responses in C57BL/6 mice. Furthermore, the NY-ESO-1 vaccine induced NY-ESO-1-specific CD8(+) CTLs in HLA-A2 transgenic mice that were capable of lysing human HLA-A2(+) NY-ESO-1(+) tumor cells. Finally, C57BL/6 mice, immunized with the NY-ESO-1 vaccine, were protected against challenge with a B16 melanoma cell line expressing NY-ESO-1. These data illustrate that the NY-ESO-1 vaccine represents a potent therapeutic anticancer vaccine.
Maraskovsky
Eugene
E
Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia. Eugene_Marakovsky@csl.com.au
Sjölander
Sigrid
S
Drane
Debbie P
DP
Schnurr
Max
M
Le
Thuy T T
TT
Mateo
Luis
L
Luft
Thomas
T
Masterman
Kelly-Anne
KA
Tai
Tsin-Yee
TY
Chen
Qiyuan
Q
Green
Simon
S
Sjölander
Anders
A
Pearse
Martin J
MJ
Lemonnier
Francois A
FA
Chen
Weisan
W
Cebon
Jonathan
J
Suhrbier
Andreas
A
D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D008546:Melanoma, Experimental; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015704:CD4 Antigens; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins