DNA vaccines against HPV-16 E7-expressing tumour cells.
BACKGROUND
Genetic immunisation induces the endogenous production of the encoded antigens, which favours their presentation by MHC class I molecules. The E7 protein from "high risk" Human Papillomavirus (HPV) is constitutively expressed in cervical cancer and represents a target for immunotherapy.


METHODS
Several E7-encoding DNA vaccines were constructed including unmodified E7 and E7 fused to ubiquitin or to the Invariant chain in order to increase the presentation of E7-derived peptides by MHC class I or II molecules, respectively. These vaccines were administered i.m. to C57BL/6 mice that were subsequently challenged with E7-positive tumour cell lines expressing different levels of MHC class I molecules.


RESULTS
The E7-Ii fusion sequence protected a number of animals from tumour challenging. No differences were associated with the MHC class I status of the challenging cell lines.


CONCLUSIONS
Engineering the intracellular pathway for antigen presentation is able to produce a valid therapeutic response even against tumours with down-regulated MHC class I.
De Marco
Federico
F
Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi D'Oro 156, 00158, Rome, Italy.
Hallez
Sophie
S
Brulet
Jean Marc
JM
Gesché
Fabienne
F
Marzano
Pasqualina
P
Flamini
Silvio
S
Marcante
Maria Luisa
ML
Venuti
Aldo
A
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002461:Cell Line, Transformed / Q000637:transplantation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G / Q000096:biosynthesis; D007273:Injections, Intramuscular; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D025801:Ubiquitin; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use*
D000912:Antibodies, Neoplasm; D000914:Antibodies, Viral; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D025801:Ubiquitin; D019444:Vaccines, DNA; C045084:invariant chain; C059731:oncogene protein E7, Human papillomavirus type 16