Abstract
HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8+ T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 472-477 |
| Number of pages | 6 |
| Journal | Journal of Immunotherapy |
| Volume | 27 |
| Issue number | 6 |
| State | Published - Nov 2004 |
| Externally published | Yes |
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Keywords
- Cancer vaccine
- HLA-A2
- HLA-DP
- NY-ESO-1
- Tumor antigens
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
- Immunology
Cite this
Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. / Khong, Hung T.; Yang, James C.; Topalian, Suzanne; Sherry, Richard M.; Mavroukakis, Sharon A.; White, Donald E.; Rosenberg, Steven A.
In: Journal of Immunotherapy, Vol. 27, No. 6, 11.2004, p. 472-477.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen
AU - Khong, Hung T.
AU - Yang, James C.
AU - Topalian, Suzanne
AU - Sherry, Richard M.
AU - Mavroukakis, Sharon A.
AU - White, Donald E.
AU - Rosenberg, Steven A.
PY - 2004/11
Y1 - 2004/11
N2 - HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8+ T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.
AB - HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8+ T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.
KW - Cancer vaccine
KW - HLA-A2
KW - HLA-DP
KW - NY-ESO-1
KW - Tumor antigens
UR - http://www.scopus.com/inward/record.url?scp=7444253937&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444253937&partnerID=8YFLogxK
M3 - Article
C2 - 15534491
AN - SCOPUS:7444253937
VL - 27
SP - 472
EP - 477
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1524-9557
IS - 6
ER -