Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution

被引:39
作者
Bownds, S [1 ]
Tong-On, P [1 ]
Rosenberg, SA [1 ]
Parkhurst, M [1 ]
机构
[1] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA
关键词
NY-ESO-1; cancer testis antigens; HLA-A2.1; cytotoxic T lymphocytes; epitope; immunotherapy;
D O I
10.1097/00002371-200101000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapies for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1(+) patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-1:157-165 but not NY-ESO-1:155-163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected fur continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1(+) patients with metastatic melanoma, NY-ESO-I:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1(+) NY-ESO-1(+) turner cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1(+) tumors.
引用
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页码:1 / 9
页数:9
相关论文
共 23 条
[1]   Identification of NY-ESO-1 peptide analogues capable of improved stimulation of tumor-reactive CTL [J].
Chen, JL ;
Dunbar, PR ;
Gileadi, U ;
Jäger, E ;
Gnjatic, S ;
Nagata, Y ;
Stockert, E ;
Panicalli, DL ;
Chen, YT ;
Knuth, A ;
Old, LJ ;
Cerundolo, V .
JOURNAL OF IMMUNOLOGY, 2000, 165 (02) :948-955
[2]  
Chen YT, 1999, CANCER J SCI AM, V5, P16
[3]   A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening [J].
Chen, YT ;
Scanlan, MJ ;
Sahin, U ;
Tureci, O ;
Gure, AO ;
Tsang, SL ;
Williamson, B ;
Stockert, E ;
Pfreundschuh, M ;
Old, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) :1914-1918
[4]  
Clay TM, 1999, J IMMUNOL, V162, P1749
[5]   Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1:: Definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes [J].
Jäger, E ;
Chen, YT ;
Drijfhout, JW ;
Karbach, J ;
Ringhoffer, M ;
Jäger, D ;
Arand, M ;
Wada, H ;
Noguchi, Y ;
Stockert, E ;
Old, LJ ;
Knuth, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (02) :265-270
[6]   Monitoring CD8 T cell responses to NY-ESO-1:: Correlation of humoral and cellular immune responses [J].
Jäger, E ;
Nagata, Y ;
Gnjatic, S ;
Wada, H ;
Stockert, E ;
Karbach, J ;
Dunbar, PR ;
Lee, SY ;
Jungbluth, A ;
Jäger, D ;
Arand, M ;
Ritter, C ;
Cerundolo, V ;
Dupont, B ;
Chen, YT ;
Old, LJ ;
Knuth, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (09) :4760-4765
[7]  
Jäger E, 1999, INT J CANCER, V84, P506, DOI 10.1002/(SICI)1097-0215(19991022)84:5<506::AID-IJC10>3.0.CO
[8]  
2-6
[9]   Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4+ T lymphocytes of patients with NY-ESO-1-expressing melanoma [J].
Jäger, E ;
Jäger, D ;
Karbach, J ;
Chen, YT ;
Ritter, G ;
Nagata, Y ;
Gnjatic, S ;
Stockert, E ;
Arand, M ;
Old, LJ ;
Knuth, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (04) :625-630
[10]  
Nishimura MI, 1999, CANCER RES, V59, P6230