title: Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen.
abstract: OBJECTIVE
  A phase I clinical trial in patients with advanced carcinoma was conducted, using a replication-defective avipox vaccine containing the gene for the human carcinoembryonic antigen (CEA). The canarypox vector, designated ALVAC, has the ability to infect human cells but cannot replicate.
  
  
  METHODS
  The recombinant vaccine, designated ALVAC-CEA, was administered intramuscularly three times at 28-day intervals. Each cohort of six patients received three doses of either 2.5 x 10(5), 2.5 x 10(6), or 2.5 x 10(7) plaque-forming units of vaccine.
  
  
  RESULTS
  The vaccine was well tolerated at all dose levels and no significant toxicity was attributed to the treatment. No objective antitumor response was observed during the trial in patients with measurable disease. Studies were conducted to assess whether ALVAC-CEA had the ability to induce cytolytic T-lymphocyte (CTL) responses in patients with advanced cancer. Peripheral blood mononuclear cells (PBMCs) from patients with the MHC class I A2 allele were obtained before vaccine administration and 1 month after the third vaccination. Peripheral blood mononuclear cells were incubated with the CEA immunodominant CTL epitope carcinoembryonic antigen peptide-1 and interleukin 2 and quantitated using CTL precursor frequency analysis. In seven of nine patients evaluated, statistically significant increases in CTL precursors specific for CEA were observed in PBMCs after vaccination, compared with before vaccination.
  
  
  CONCLUSIONS
  These studies constitute the first phase I trial of an avipox recombinant in cancer patients. The recombinant vaccine ALVAC-CEA seems to be safe and has been demonstrated to elicit CEA-specific CTL responses. These studies thus form the basis for the further clinical exploration of the ALVAC-CEA recombinant vaccine in phase I/II studies in protocols designed to enhance the generation of human T-cell responses to CEA.
authors.affiliation: Georgetown University Medical Center, Vincent T. Lombardi Cancer Center, Washington, DC 20007, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Marshall
authors.forename: M J
authors.initials: MJ
authors.lastname: Hawkins
authors.forename: K Y
authors.initials: KY
authors.lastname: Tsang
authors.forename: E
authors.initials: E
authors.lastname: Richmond
authors.forename: J E
authors.initials: JE
authors.lastname: Pedicano
authors.forename: M Z
authors.initials: MZ
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018150:Avipoxvirus; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D014614:Vaccines, Synthetic