Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope.
The potency of DNA vaccines may be affected by the efficiency of intracellular processing and MHC class I presentation of encoded antigens. Since a single-chain trimer (SCT) composed of peptide, beta2-microglobulin (beta2m), and MHC class I heavy chain has been shown to bypass antigen processing and lead to stable presentation of peptides, we investigated the efficacy of a DNA vaccine encoding a SCT composed of an immunodominant CTL epitope of human papillomavirus type 16 (HPV-16) E6 antigen, beta2m, and H-2Kb MHC class I heavy chain (pIRES-E6-beta2m-Kb). Transfection of 293 cells with pIRES-E6-beta2m-Kb can bypass antigen processing and lead to stable presentation of E6 peptide. Furthermore, C57BL/6 mice vaccinated with pIRES-E6-beta2m-Kb exhibited significantly increased E6 peptide-specific CD8+ T-cell immune responses compared to mice vaccinated with DNA encoding wild-type E6. Most importantly, 100% of mice vaccinated with pIRES-E6-beta2m-Kb DNA were protected against a lethal challenge of E6-expressing TC-1 tumor cells. In contrast, all mice vaccinated with wild-type E6 DNA or control plasmid DNA grew tumors. Our data indicate that a DNA vaccine encoding a SCT can lead to stable enhanced MHC class I presentation of encoded antigenic peptide and may be useful for improving DNA vaccine potency to control tumors or infectious diseases.
Huang
C-H
CH
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Peng
S
S
He
L
L
Tsai
Y-C
YC
Boyd
D A K
DA
Hansen
T H
TH
Wu
T-C
TC
Hung
C-F
CF
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000628:therapy; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014183:Transplantation, Heterologous
D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins