Anchoring cytokines to tumor cells for the preparation of anticancer vaccines without gene transfection in mice.
The authors have investigated a new way of combining cytokines with tumor cells to prepare anticancer vaccines. This method may offer an alternative to gene therapy approaches. It consists in anchoring recombinant cytokines to the cell membrane. Attachment is mediated by the transmembrane domain of diphtheria toxin (T) genetically fused to the cytokine and is triggered by an acid pH pulse. The authors found that the fusion protein T-hIL-2 anchored to the surface of tumor cells retained its IL-2 activity while remaining exposed for several days. Interestingly, vaccination of mice with these modified tumor cells induced a protective antitumor immunity mediated by tumor-specific cytotoxic T lymphocytes. This procedure presents several advantages as compared with the conventional approaches based on the transfection of tumor cells with cytokine genes. It does not require the culture of tumor cells from the patients and the selection of transfected clones, it eliminates the safety problems connected with viral vectors, and it allows the control of the amount of cytokines delivered with the vaccine.
Nizard
Philippe
P
Département d'Ingénierie et d'Etudes des Protéines, CEA-Saclay, France.
Gross
David Alexandre
DA
Babon
Aurélie
A
Chenal
Alexandre
A
Beaumelle
Bruno
B
Kosmatopoulos
Konstadinos
K
Gillet
Daniel
D
D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D004167:Diphtheria Toxin / Q000235:genetics / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D016207:Cytokines; D004167:Diphtheria Toxin; D007376:Interleukin-2