title: A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients.
abstract: OBJECTIVE
  Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine.
  
  
  METHODS
  Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer overexpressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles.
  
  
  RESULTS
  Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively.
  
  
  CONCLUSIONS
  We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
authors.affiliation: Vaccine Branch, CCR, NCI, 41 Medlars Dr., Building 41 Room B900, Bethesda, MD 20892, USA.
authors.forename: Osama E
authors.initials: OE
authors.lastname: Rahma
authors.forename: Ed
authors.initials: E
authors.lastname: Ashtar
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czystowska
authors.forename: Marta E
authors.initials: ME
authors.lastname: Szajnik
authors.forename: Eva
authors.initials: E
authors.lastname: Wieckowski
authors.forename: Sarah
authors.initials: S
authors.lastname: Bernstein
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Herrin
authors.forename: Mortada A
authors.initials: MA
authors.lastname: Shams
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Carmen
authors.initials: C
authors.lastname: Visus
authors.forename: Albert B
authors.initials: AB
authors.lastname: Deleo
authors.forename: Judith K
authors.initials: JK
authors.lastname: Wolf
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Bell
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005221:Fatigue / Q000209:etiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008231:Lymphopenia / Q000209:etiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D016159:Tumor Suppressor Protein p53; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor