Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: a phase I escalating-dose trial.
The safety and immunogenicity of the human papillomavirus type 16 (HPV16) or HPV18 (HPV16/18) E7 antigen-pulsed mature dendritic cell (DC) vaccination were evaluated for patients with stage IB or IIA cervical cancer. Escalating doses of autologous DC (5, 10, and 15 x 10(6) cells for injection) were pulsed with recombinant HPV16/18 E7 antigens and keyhole limpet hemocyanin (KLH; an immunological tracer molecule) and delivered in five subcutaneous injections at 21-day intervals to 10 cervical cancer patients with no evidence of disease after they underwent radical surgery. Safety, toxicity, delayed-type hypersensitivity (DTH) reaction, and induction of serological and cellular immunity against HPV16/18 E7 and KLH were monitored. DC vaccination was well tolerated, and no significant toxicities were recorded. All patients developed CD4(+) T-cell and antibody responses to DC vaccination, as detected by enzyme-linked immunosorbent spot (ELISpot) and enzyme-linked immunosorbent assays (ELISA), respectively, and 8 out of 10 patients demonstrated levels of E7-specific CD8(+) T-cell counts, detected by ELISpot during or immediately after immunization, that were increased compared to prevaccination baseline levels. The vaccine dose did not predict the magnitude of the antibody or T-cell response or the time to detection of HPV16/18 E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen and KLH were detected for all patients after vaccination. We conclude that HPV E7-loaded DC vaccination is safe and immunogenic for stage IB or IIA cervical cancer patients. Phase II E7-pulsed DC-based vaccination trials with cervical cancer patients harboring a limited tumor burden, or who are at significant risk of tumor recurrence, are warranted.
UAMS Medical Center, Division of Gynecologic Oncology, University of Arkansas, 4301 W. Markham, Little Rock, AR 72205-7199, USA. santinalessandrod@uams.edu
Alessandro D
AD
Santin
Stefania
S
Bellone
Michela
M
Palmieri
Alessandro
A
Zanolini
Antonella
A
Ravaggi
Eric R
ER
Siegel
Juan J
JJ
Roman
Sergio
S
Pecorelli
Martin J
MJ
Cannon
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014611:Vaccination
D000914:Antibodies, Viral; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin