Liposomal transfection of squamous carcinoma cells of the head and neck with IL-2 and B7 plasmids inducing an autologous immune response in vitro.
New treatment strategies need to be developed to face the increasing incidence and mortality of squamous cell carcinoma of the head and neck (SCCHN), as the overall survival rate remains poor, with minor therapeutic progress having been achieved over the past forty years. One major goal could be to restore a damaged immune system by intratumoral injection of IL-2-genes that permanently provide non-toxic IL-2-protein concentrations at the tumor site, sufficient to activate cellular immunity in vivo. We showed that the transfection of SCCHN cell lines with IL-2-plasmids, encapsulated in DOTMA/Col, in vitro resulted in the synthesis of bioactive IL-2-protein for up to 30 days by the tumor cells themselves. The transcription of secondary cytokines (IL-6, IL-8, GM-CSF, TNF-alpha) and the expression of immunomodulatory surface molecules (MHC Class II, ICAM1) were enhanced. The IL-2-modified tumor cells were effectively lysed by autologous peripheral blood lymphocytes (PBLs). The immune response was enhanced by B7.1-gene-cotransfection and/or preactivation of PBLs with exogenous IL-2. We demonstrated that in vitro liposome-mediated IL-2-gene-transfection of SCCHN cells is an effective method to stimulate an autologous immune response and is, therefore, promising for clinical application.
Mayer
Anna
A
GSF-National Research Center for Environment and Health, Department of Comparative Medicine, Neuherberg, Germany.
Andratschke
Michaela
M
Pauli
Christof
C
Reitberger
Eva
E
Kolbow
Kristina
K
Wollenberg
Barbara
B
D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D014158:Transcription, Genetic; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D018122:B7-1 Antigen; C090509:Icam1 protein, mouse; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D014409:Tumor Necrosis Factor-alpha; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002784:Cholesterol