Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100

被引:83
作者
Zhai, YF [1 ]
Yang, JC [1 ]
Spiess, P [1 ]
Nishimura, MI [1 ]
Overwijk, WW [1 ]
Roberts, B [1 ]
Restifo, NP [1 ]
Rosenberg, SA [1 ]
机构
[1] GENZYME CORP,FRAMINGHAM,MA 01701
来源
JOURNAL OF IMMUNOTHERAPY | 1997年 / 20卷 / 01期
关键词
cancer vaccine; in vivo model; B16; melanoma; adenovirus; vaccinia virus;
D O I
10.1097/00002371-199701000-00002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The recent identification of genes encoding melanoma-associated antigens has opened new possibilities for the development of cancer vaccines designed to cause the rejection of established tumors. To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library. The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins. Comparison of the DNA sequences of the murine MART1 genes, derived from normal melanocytes, the immortalized nontumorgenic melanocyte line Melan-a and the B16 melanoma, showed all to be identical. Northern and Western blot analyses confirmed that both genes encoded products that were melanocyte lineage proteins. Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma. In contrast, immunization of mice with human gp100 using recombinant adenoviruses elicited T cells specific for hgp100. but these T cells also cross reacted with B16 tumor in vitro and induced significant but weak protection against B16 challenge. Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma. These results may suggest that immunization with heterologous tumor antigen, rather than self, may be more effective as an immunotherapeutic reagent in designing antigen-specific cancer vaccines.
引用
收藏
页码:15 / 25
页数:11
相关论文
共 28 条
  • [1] BOCKENSTEDT LK, 1995, J IMMUNOL, V154, P3516
  • [2] BOON T, 1994, IMPORTANT ADV ONCOLO, P58
  • [3] THE TYROSINASE GENE CODES FOR AN ANTIGEN RECOGNIZED BY AUTOLOGOUS CYTOLYTIC T-LYMPHOCYTES ON HLA-A2 MELANOMAS
    BRICHARD, V
    VANPEL, A
    WOLFEL, T
    WOLFEL, C
    DEPLAEN, E
    LETHE, B
    COULIE, P
    BOON, T
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (02) : 489 - 495
  • [4] A NEW GENE CODING FOR A DIFFERENTIATION ANTIGEN RECOGNIZED BY AUTOLOGOUS CYTOLYTIC T-LYMPHOCYTES ON HLA-A2 MELANOMAS
    COULIE, PG
    BRICHARD, V
    VANPEL, A
    WOLFEL, T
    SCHNEIDER, J
    TRAVERSARI, C
    MATTEI, S
    DEPLAEN, E
    LURQUIN, C
    SZIKORA, JP
    RENAULD, JC
    BOON, T
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (01) : 35 - 42
  • [5] CANCER ANTIGENS - IMMUNE RECOGNITION OF SELF AND ALTERED SELF
    HOUGHTON, AN
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (01) : 1 - 4
  • [6] IDENTIFICATION OF A HUMAN-MELANOMA ANTIGEN RECOGNIZED BY TUMOR-INFILTRATING LYMPHOCYTES ASSOCIATED WITH IN-VIVO TUMOR REJECTION
    KAWAKAMI, Y
    ELIYAHU, S
    DELGADO, CH
    ROBBINS, PF
    SAKAGUCHI, K
    APPELLA, E
    YANNELLI, JR
    ADEMA, GJ
    MIKI, T
    ROSENBERG, SA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (14) : 6458 - 6462
  • [7] IDENTIFICATION OF THE IMMUNODOMINANT PEPTIDES OF THE MART-1 HUMAN-MELANOMA ANTIGEN RECOGNIZED BY THE MAJORITY OF HLA-A2-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES
    KAWAKAMI, Y
    ELIYAHU, S
    SAKAGUCHI, K
    ROBBINS, PF
    RIVOLTINI, L
    YANNELLI, JR
    APPELLA, E
    ROSENBERG, SA
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (01) : 347 - 352
  • [8] CLONING OF THE GENE CODING FOR A SHARED HUMAN-MELANOMA ANTIGEN RECOGNIZED BY AUTOLOGOUS T-CELLS INFILTRATING INTO TUMOR
    KAWAKAMI, Y
    ELIYAHU, S
    DELGADO, CH
    ROBBINS, PF
    RIVOLTINI, L
    TOPALIAN, SL
    MIKI, T
    ROSENBERG, SA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) : 3515 - 3519
  • [9] KAWAKAMI Y, 1995, J IMMUNOL, V154, P3961
  • [10] KOBAYASHI T, 1994, J BIOL CHEM, V269, P29198