Gene therapy of B-cell lymphoma with cytokine gene-modified trioma cells.
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.
Strehl
J
J
GSF-Institut für Molekulare Immunologie, Munich, Germany.
Selmayr
M
M
Kremer
J P
JP
Hültner
L
L
Lindhofer
H
H
Mocikat
R
R
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D019496:Cancer Vaccines; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D019496:Cancer Vaccines; D016207:Cytokines; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor