Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2.
RNA-based genetic immunization represents an alternative novel strategy for antigen-specific cancer vaccines. In the present paper we investigate the use of synthetic messenger RNA in an experimental melanoma model. We show that gene gun-based immunization using synthetic RNA mediates gene expression in the epidermis and effectively induces antigen-specific cellular and humoral immunity in mice in vivo. Importantly, bombardment of the skin with RNA coding for the melanocytic self-antigen TRP2 linked to the immunogenic protein EGFP was associated with protection against experimentally induced B16 melanoma lung metastases and vitiligo-like fur depigmentation. Our results provide a scientific basis for clinical trials using synthetic mRNA encoding melanocytic antigens linked to immunogenic helper proteins for vaccination of patients with melanoma.
Steitz
Julia
J
Department of Dermatology, Laboratory of Experimental Dermatology, Rheinische Friedrich Wilhelm University, Sigmund Freud Str. 25, 53105, Bonn, Germany.
Britten
Cedrik M
CM
Wölfel
Thomas
T
Tüting
Thomas
T
D000818:Animals; D019470:Biolistics; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014820:Vitiligo; D001616:beta-Galactosidase / Q000235:genetics
D019496:Cancer Vaccines; D008565:Membrane Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C113139:Trp2 protein, vertebrate; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase