Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer.
NY-ESO-1 is a "cancer-testis" antigen expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. The NY-ESO-1 peptide epitope, ESO(157-170), is recognized by HLA-DP4-restricted CD4+ T cells and HLA-A2- and A24-restricted CD8+ T cells. To test whether providing cognate helper CD4+ T cells would enhance the antitumor immune response, we conducted a phase I clinical trial of immunization with ESO(157-170) mixed with incomplete Freund's adjuvant (Montanide ISA51) in 18 HLA-DP4+ EOC patients with minimal disease burden. NY-ESO-1-specific Ab responses and/or specific HLA-A2-restricted CD8+ and HLA-DP4-restricted CD4+ T cell responses were induced by a course of at least five vaccinations at three weekly intervals in a high proportion of patients. There were no serious vaccine-related adverse events. Vaccine-induced CD8+ and CD4+ T cell clones were shown to recognize NY-ESO-1-expressing tumor targets. T cell receptor analysis indicated that tumor-recognizing CD4+ T cell clones were structurally distinct from non-tumor-recognizing clones. Long-lived and functional vaccine-elicited CD8+ and CD4+ T cells were detectable in some patients up to 12 months after immunization. These results confirm the paradigm that the provision of cognate CD4+ T cell help is important for cancer vaccine design and provides the rationale for a phase II study design using ESO(157-170) epitope or the full-length NY-ESO-1 protein for immunotherapy in patients with EOC.
Odunsi
Kunle
K
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. kunle.odunsi@@roswellpark.org
Qian
Feng
F
Matsuzaki
Junko
J
Mhawech-Fauceglia
Paulette
P
Andrews
Christopher
C
Hoffman
Eric W
EW
Pan
Linda
L
Ritter
Gerd
G
Villella
Jeannine
J
Thomas
Bridget
B
Rodabaugh
Kerry
K
Lele
Shashikant
S
Shrikant
Protul
P
Old
Lloyd J
LJ
Gnjatic
Sacha
S
D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C522785:peptide NY-ESO-1 157-170; D005620:Freund's Adjuvant