Gene therapy of B-cell lymphoma with cytokine gene-modified trioma cells

Int J Cancer. 1999 Sep 24;83(1):113-20. doi: 10.1002/(sici)1097-0215(19990924)83:1<113::aid-ijc20>3.0.co;2-j.

Abstract

The trioma approach is a new immunotherapeutic strategy for treating B-cell lymphomas. It is based on converting the tumour idiotype to a bispecific immunoglobulin that redirects the idiotype to antigen-presenting cells. We show here that even pre-existing tumours can be eradicated by trioma vaccination, that the trioma approach is superior to vaccination with cytokine gene-modified autologous tumour cells and that there is a synergism between trioma immunisation and GM-CSF gene transfer. Furthermore, we show that the immunising potential of GM-CSF gene-modified autologous lymphoma cells is not as dependent on the cytokine expression level as described for other tumour models, such that even minute expression rates are effective. IL-4 gene transfer in the lymphoma model is considerably less efficient or even ineffective when more sensitive systems are used. Remarkably, trioma-mediated effects are extinguished when IL-4 is expressed by the trioma cell.

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology
  • Antigen-Presenting Cells / immunology
  • Cancer Vaccines
  • Cloning, Molecular
  • Cytokines / genetics*
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Therapy / methods*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antibodies, Bispecific
  • Cancer Vaccines
  • Cytokines
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor