[Anchoring cytokines to cancer cells using diphtheria toxin: better than immunotherapy by gene transfer?].
Many cytokines are able to stimulate the antitumor immune response. However, in order to avoid the toxic effects due to systemic injection, it is necessary to concentrate the cytokines in the tumor microenvironment. Current methods, based on the transfer of cytokine genes into tumor cells, still suffer drawbacks. We describe an alternative approach using recombinant cytokines genetically conjugated to a membrane anchor derived from diphtheria toxin. Interleukin-2 anchored to lymphoma and melanoma cells remained displayed on their surface and were not internalized. Injection of these cell preparations to mice led to an immune response able to prevent or slow tumor growth following tumor challenge.
Nizard
P
P
Département d'Ingénierie et d'Etudes des Protéines, CEA-Saclay, 91191 Gif-sur-Yvette, France.
Gross
D A
DA
Chenal
A
A
Beaumelle
B
B
Kosmatopoulos
K
K
Gillet
D
D
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000008:administration & dosage* / Q000235:genetics; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000235:genetics; D016503:Drug Delivery Systems; D006801:Humans; D016233:Immunotherapy, Active; D008223:Lymphoma / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000628:therapy* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins; D014162:Transfection
D016207:Cytokines; D004167:Diphtheria Toxin; D011993:Recombinant Fusion Proteins