title: Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma.
abstract: OBJECTIVE
  Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points.
  
  
  METHODS
  We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination.
  
  
  RESULTS
  The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis.
  
  
  CONCLUSIONS
  This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Junko
authors.initials: J
authors.lastname: Yokokawa
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Poole
authors.forename: Cinzia
authors.initials: C
authors.lastname: Remondo
authors.forename: Vittore
authors.initials: V
authors.lastname: Cereda
authors.forename: Jacquin L
authors.initials: JL
authors.lastname: Jones
authors.forename: Mary P
authors.initials: MP
authors.lastname: Pazdur
authors.forename: Jack P
authors.initials: JP
authors.lastname: Higgins
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Herbert
authors.initials: H
authors.lastname: Kotz
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018122:B7-1 Antigen / Q000276:immunology / Q000627:therapeutic use; D018968:CD58 Antigens / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D011212:Poxviridae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D018968:CD58 Antigens; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C060192:MUC1 protein, human; D018396:Mucin-1; D014614:Vaccines, Synthetic; D018799:Intercellular Adhesion Molecule-1