Oral DNA vaccination: antigen uptake and presentation by dendritic cells elicits protective immunity.
Melanoma differentiation antigens, such as glycoprotein 100 (gp100), have been shown to induce both cellular and humoral immune responses against melanoma in mouse and man. They are therefore considered as potential targets for melanoma immunotherapy. In this study, we have used the attenuated auxotrophic mutant strain SL7207 of Salmonella typhimurium as vehicle for a human gp100 (hgp100) DNA vaccine against melanoma. In vitro studies indicate that Salmonella/pCMV-hgp100 is efficiently scavenged by dendritic cells, resulting in the expression of the hgp100 transcription unit in the DC. In addition, oral administration of Salmonella/pCMV-hgp100 results in the expression of hgp100 RNA and protein by cells exhibiting DC-morphology in mesenteric lymph nodes as soon as 3 days after vaccination. Analysis of the efficacy of the Salmonella/pCMV-hgp100 vaccine in the B16/hgp100 model demonstrated the induction of strong anti-hgp100 CTL responses and protective immunity in 70% of the vaccinated mice, but not in control mice. Based on these data, we consider S. typhimurium as a useful vehicle for the design of recombinant DNA based anti-cancer vaccines.
Cochlovius
Björn
B
Division of Diagnostics and Experimental Therapy, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. b.cochlovius@dkfz.de
Stassar
Marike J J G
MJ
Schreurs
Marco W
MW
Benner
Axel
A
Adema
Gosse J
GJ
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D012486:Salmonella typhimurium / Q000276:immunology; D015996:Survival Rate; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014820:Vitiligo; D058951:gp100 Melanoma Antigen
D000941:Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D012333:RNA, Messenger; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen