Immunological gene therapy with ex vivo gene-modified tumor cells:: A critique and a reappraisal

被引:67
作者
Parmiani, G [1 ]
Rodolfo, M [1 ]
Melani, C [1 ]
机构
[1] Ist Nazl Tumori, Gene Therapy Program, I-20133 Milan, Italy
关键词
D O I
10.1089/10430340050032375
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Studies using animal models have demonstrated that transduction of genes encoding different cytokines into tumor cells results in a local recruitment of inflammatory cells that in turn can inhibit tumor growth. This is often accompanied by tumor antigen priming of the host immune system, which becomes resistant to subsequent challenge by the parental, untransduced tumor. Gene-transduced tumor cells have therefore been widely used as vaccines, although in the therapeutic setting their antitumor efficacy was limited to a few animal models. On the basis of this rationale, clinical studies were initiated, results of which are evaluated in this review to identify the reasons for their limited efficacy. We point out problems generated by the use of autologous versus allogeneic gene-transduced vaccines, by the choice of the appropriate cytokine(s), and by patient selection. Results of these studies are also compared with those obtained by peptide-based vaccines in similar groups of patients. Altogether, we conclude that improvements can be made in the construction of gene-modified vaccines by (1) using tumor cells known to express molecularly defined antigens, (2) introducing, in addition to genes encoding cytokines, genes encoding T cell costimulatory molecules, (3) increasing the amount of cytokine released locally by irradiated cells, and (4) coadministering adjuvant cytokines (IL-2 and IL-12) systemically in order to expand the T cell pool activated by vaccines.
引用
收藏
页码:1269 / 1275
页数:7
相关论文
共 50 条
  • [1] ALLIONE A, 1994, CANCER RES, V54, P6022
  • [2] An expanded peripheral T cell population to a cytotoxic T lymphocyte (CTL)-defined, melanocyte-specific antigen in metastatic melanoma patients impacts on generation of peptide-specific CTLs but does not overcome tumor escape from immune surveillance in metastatic lesions
    Anichini, A
    Molla, A
    Mortarini, R
    Tragni, G
    Bersani, I
    Di Nicola, M
    Gianni, AM
    Pilotti, S
    Dunbar, R
    Cerundolo, V
    Parmiani, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (05) : 651 - 667
  • [3] Vaccination of melanoma patients with interleukin 4 gene-transduced allogeneic melanoma cells
    Arienti, F
    Belli, F
    Napolitano, F
    Sulé-Suso, J
    Mazzocchi, A
    Gallino, GF
    Cattelan, A
    Sanantonio, C
    Rivoltini, L
    Melani, C
    Colombo, MP
    Cascinelli, N
    Maio, M
    Parmiani, G
    [J]. HUMAN GENE THERAPY, 1999, 10 (18) : 2907 - 2916
  • [4] INTERLEUKIN-2 GENE-TRANSDUCED HUMAN-MELANOMA CELLS EFFICIENTLY STIMULATE MHC-UNRESTRICTED AND MHC-RESTRICTED AUTOLOGOUS LYMPHOCYTES
    ARIENTI, F
    SULESUSO, J
    MELANI, C
    MACCALLI, C
    BELLI, F
    ILLENI, MT
    ANICHINI, A
    CASCINELLI, N
    COLOMBO, MP
    PARMIANI, G
    [J]. HUMAN GENE THERAPY, 1994, 5 (09) : 1139 - 1150
  • [5] Limited antitumor T cell response in melanoma patients vaccinated with interleukin-2 gene-transduced allogeneic melanoma cells
    Arienti, F
    SuleSuso, J
    Belli, F
    Mascheroni, L
    Rivoltini, L
    Melani, C
    Maio, M
    Cascinelli, N
    Colombo, MP
    Parmiani, G
    [J]. HUMAN GENE THERAPY, 1996, 7 (16) : 1955 - 1963
  • [6] BASOMBRIO MA, 1970, CANCER RES, V30, P2458
  • [7] IL-2 adenovector-transduced autologous tumor cells reduce antitumor immune responses in patients with neuroblastoma
    Bowman, L
    Grossmann, M
    Rill, D
    Brown, M
    Zhong, WY
    Alexander, B
    Leimig, T
    Coustan-Smith, E
    Campana, D
    Jenkins, J
    Woods, D
    Kitchingman, G
    Vanin, E
    Brenner, M
    [J]. BLOOD, 1998, 92 (06) : 1941 - 1949
  • [8] Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed neuroblastoma
    Bowman, LC
    Grossmann, M
    Rill, D
    Brown, M
    Zhong, WY
    Alexander, B
    Leimig, T
    Coustan-Smith, E
    Campana, D
    Jenkins, J
    Woods, D
    Brenner, M
    [J]. HUMAN GENE THERAPY, 1998, 9 (09) : 1303 - 1311
  • [9] LOCAL-ADMINISTRATION OF CELLS CONTAINING AN INSERTED IL-2 GENE AND PRODUCING IL-2 INHIBITS GROWTH OF HUMAN-TUMORS IN NU NU MICE
    BUBENIK, J
    VOITENOK, NN
    KIELER, J
    PRASSOLOV, VS
    CHUMAKOV, PM
    BUBENIKOVA, D
    SIMOVA, J
    JANDLOVA, T
    [J]. IMMUNOLOGY LETTERS, 1988, 19 (04) : 279 - 282
  • [10] Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12
    Cavallo, F
    Signorelli, P
    Giovarelli, M
    Musiani, P
    Modesti, A
    Brunda, MJ
    Colombo, MP
    Forni, G
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (14) : 1049 - 1058