Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.
OBJECTIVE
Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins.


METHODS
Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus.


RESULTS
Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses.


CONCLUSIONS
This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.
Kaufmann
Andreas M
AM
Frauenklinik, Friedrich-Schiller-University of Jena, 07743 Jena, Germany. a.kaufmann@med.uni-jena.de
Stern
Peter L
PL
Rankin
Elaine M
EM
Sommer
Harald
H
Nuessler
Volkmar
V
Schneider
Achim
A
Adams
Malcom
M
Onon
Toli S
TS
Bauknecht
Thomas
T
Wagner
Uwe
U
Kroon
Karlijn
K
Hickling
Julian
J
Boswell
Christopher M
CM
Stacey
Simon N
SN
Kitchener
Henry C
HC
Gillard
Jennifer
J
Wanders
Jantien
J
Roberts
John St C
JS
Zwierzina
Heinz
H
D000230:Adenocarcinoma / Q000517:prevention & control / Q000821:virology; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control / Q000821:virology; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005838:Genotype; D015788:HLA-A1 Antigen / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000627:therapeutic use*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins; D016036:Seroepidemiologic Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014412:Tumor Virus Infections / Q000517:prevention & control* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000627:therapeutic use; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control / Q000821:virology
D000914:Antibodies, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D015788:HLA-A1 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C100344:human papillomavirus vaccine, TA; C059731:oncogene protein E7, Human papillomavirus type 16