Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer Journal Article
| Authors: | Odunsi, K.; Qian, F.; Matsuzaki, J.; Mhawech-Fauceglia, P.; Andrews, C.; Hoffman, E. W.; Pan, L.; Ritter, G.; Villella, J.; Thomas, B.; Rodabaugh, K.; Lele, S.; Shrikant, P.; Old, L. J.; Gnjatic, S. |
| Article Title: | Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer |
| Abstract: | 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, ESO157-170, 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 ESO157-170 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. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: | clinical article; clinical trial; antigen expression; cd8+ t lymphocyte; t lymphocyte; ovarian neoplasms; t-lymphocytes; cancer immunotherapy; ovary cancer; neoplasm proteins; drug specificity; drug hypersensitivity; drug receptor binding; t lymphocyte receptor; immune response; cancer vaccine; cancer vaccines; ny eso 1 antigen; hla antigen class 2; antigen recognition; cd4+ t lymphocyte; peptide fragments; epitope; hla antigen class 1; histocompatibility antigens class i; injection site pain; phase 1 clinical trial; antibodies; histocompatibility antigens class ii; humoral immunity; vaccine; antibody formation; helper cell; immunization; hla a2 antigen; freund's adjuvant; freund adjuvant; hla-dp4; peptide epitope; tumor recognition; hla a24 antigen |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 104 |
| Issue: | 31 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2007-07-31 |
| Start Page: | 12837 |
| End Page: | 12842 |
| Language: | English |
| DOI: | 10.1073/pnas.0703342104 |
| PUBMED: | 17652518 |
| PROVIDER: | scopus |
| PMCID: | PMC1937553 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 74" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work