Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens.
Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical intraepithelial neoplasia (CIN) and cancer. A newly designed vaccine, comprising the HPV16 L2, E6 and E7 as a single fusion protein (TA-CIN), was shown to elicit HPV16-specific CTL, T-helper cells and antibodies in a pre-clinical mouse model. These immune responses effectively prevented outgrowth of HPV16-positive tumour cells in a prophylactic setting as well as in a minimal residual disease setting. CTL immunity was optimally induced when TA-CIN was employed in heterologous prime-boost regimens in combination with TA-HPV, a clinical grade vaccinia-based vaccine. These data provide a scientific basis for the use of TA-CIN, alone or in combination with TA-HPV in future human trials.
van der Burg
S H
SH
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Building 1, E3-Q, PO Box 9600, 2300 RC Leiden, The Netherlands. shvdburg@worldonline.nl
Kwappenberg
K M
KM
O'Neill
T
T
Brandt
R M
RM
Melief
C J
CJ
Hickling
J K
JK
Offringa
R
R
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity*; D002213:Capsid / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity*; D036022:Capsid Proteins; D002460:Cell Line; D002461:Cell Line, Transformed; D004353:Drug Evaluation, Preclinical; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity*; D022282:Vaccines, Acellular / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control / Q000628:therapy / Q000821:virology
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019496:Cancer Vaccines; D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D022282:Vaccines, Acellular; C059731:oncogene protein E7, Human papillomavirus type 16