title: Allogeneic vaccination with a B7.1 HLA-A gene-modified adenocarcinoma cell line in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non-small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease.
  
  
  METHODS
  We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 x 10(7) cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100.
  
  
  RESULTS
  Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response.
  
  
  CONCLUSIONS
  Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.
authors.affiliation: Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, 1475 NW 12 Ave # 3510, Miami, FL 33136, USA. lraez@med.miami.edu
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cassileth
authors.forename: James J
authors.initials: JJ
authors.lastname: Schlesselman
authors.forename: Kasi
authors.initials: K
authors.lastname: Sridhar
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Eva Z
authors.initials: EZ
authors.lastname: Fisher
authors.forename: Paulette A
authors.initials: PA
authors.lastname: Baldie
authors.forename: Eckhard R
authors.initials: ER
authors.lastname: Podack
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology; D000368:Aged; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D015234:HLA-A Antigens