Chemically synthesized protein as tumour-specific vaccine: immunogenicity and efficacy of synthetic HPV16 E7 in the TC-1 mouse tumour model.
Many successful candidate vaccines capable of combating tumours in animal models come to an untimely end because of the costs associated with the approval and production of the GMP-grade materials, which are usually of biological origin, for use in humans. We have used a GMP-compatible method to chemically synthesize a pure synthetic E7 protein of the human papillomavirus type 16 (HPV16-E7). This oncogen-derived protein is constitutively expressed in cervical cancer and its precursors and is thus considered as an excellent target for tumour-specific immunity. Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens. Our results demonstrate the potential use of pure synthetic vaccines that can be efficiently produced under GMP at low cost, which will stimulate the translation of new vaccination strategies into phase I/II clinical trials.
Welters
Marij J P
MJ
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Filippov
Dmitri V
DV
van den Eeden
Susan J F
SJ
Franken
Kees L M C
KL
Nouta
Jan
J
Valentijn
A Rob P M
AR
van der Marel
Gijs A
GA
Overkleeft
Hermen S
HS
Lipford
Grayson
G
Offringa
Rienk
R
Melief
Cornelis J M
CJ
van Boom
Jacques H
JH
van der Burg
Sjoerd H
SH
Drijfhout
Jan Wouter
JW
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000138:chemical synthesis / Q000276:immunology*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000276:immunology
D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma