Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX adjuvant in women with cervical intraepithelial neoplasia.
OBJECTIVE
Persistent infection of cervical epithelium with "high risk" human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX adjuvant (HPV16 Immunotherapeutic) for patients with CIN.


METHODS
Patients with CIN (n = 31) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy.


RESULTS
Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients.


CONCLUSIONS
The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX adjuvant is safe and induces vaccine antigen specific cell mediated immunity.
Frazer
Ian H
IH
Centre for Immunology and Cancer Research, The University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia. ifrazer@cicr.uq.edu.au
Quinn
Michael
M
Nicklin
Jim L
JL
Tan
Jeffrey
J
Perrin
Lew C
LC
Ng
Peng
P
O'Connor
Vivienne M
VM
White
Olivia
O
Wendt
Ngaire
N
Martin
Juliet
J
Crowley
Jayne M
JM
Edwards
Stirling J
SJ
McKenzie
Andrew W
AW
Mitchell
Susan V
SV
Maher
Darryl W
DW
Pearse
Martin J
MJ
Basser
Russell L
RL
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002784:Cholesterol / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D010743:Phospholipids / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D012097:Repressor Proteins / Q000235:genetics; D012503:Saponins / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000628:therapy* / Q000821:virology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D004338:Drug Combinations; C068651:E6 protein, Human papillomavirus type 16; C493786:ISCOMATRIX; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D012503:Saponins; C059731:oncogene protein E7, Human papillomavirus type 16; D002784:Cholesterol