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.
Santin
Alessandro D
AD
UAMS Medical Center, Division of Gynecologic Oncology, University of Arkansas, 4301 W. Markham, Little Rock, AR 72205-7199, USA. santinalessandrod@uams.edu
Bellone
Stefania
S
Palmieri
Michela
M
Zanolini
Alessandro
A
Ravaggi
Antonella
A
Siegel
Eric R
ER
Roman
Juan J
JJ
Pecorelli
Sergio
S
Cannon
Martin J
MJ
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