title: Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer.
abstract: BACKGROUND
  The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets.
  
  
  METHODS
  Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (Arm A) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells".
  
  
  RESULTS
  51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II.
  
  
  CONCLUSIONS
  We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.
authors.forename: Osama E
authors.initials: OE
authors.lastname: Rahma
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Herrin
authors.forename: Rami A
authors.initials: RA
authors.lastname: Ibrahim
authors.forename: Anton
authors.initials: A
authors.lastname: Toubaji
authors.forename: Sarah
authors.initials: S
authors.lastname: Bernstein
authors.forename: Omar
authors.initials: O
authors.lastname: Dakheel
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Rasha
authors.initials: R
authors.lastname: Abu Eid
authors.forename: Mikayel
authors.initials: M
authors.lastname: Mkrtichyan
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.affiliation: Cancer Vaccine Branch, CCR, NCI, 10 Center Drive, Bethesda 20892, MD, USA. skhleif@gru.edu.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage* / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage* / Q000276:immunology; D012097:Repressor Proteins / Q000008:administration & dosage* / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16