title: INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect.
abstract: BACKGROUND
  Novel approaches are needed for patients with small cell lung cancer (SCLC), as response after relapse is poor with standard therapies. p53 gene mutations often occur, resulting in tumoral protein overexpression and allowing for their recognition by p53-specific cytotoxic T cells.
  
  
  METHODS
  We describe the characteristics and manufacturing of INGN-225, a p53-modified adenovirus-tranduced dendritic cell vaccine, and review available data, to understand INGN-225's role in SCLC treatment. We discuss our pre-clinical, early Phase I/II, and ongoing randomized Phase II studies.
  
  
  RESULTS
  INGN-225 was well tolerated (all toxicities <or=grade 2) in the Phase I/II trial (54 patients receiving at least 1 dose). Specific anti-p53 immune response was positive in 18/43 (41.8%) patients, with overall post-INGN-225 response observed in 17/33 (51.5%) and immune response data available in 29 (14 positive, 15 negative). Post-INGN-225 response was observed in 11/14 (78.6%) and 5/15 (33%) patients with positive and negative immune responses, respectively.
  
  
  CONCLUSIONS
  INGN-225 is safe, induces a significant immune response, and appears to sensitize SCLC to subsequent chemotherapy. Improvements in immune response induction and understanding the chemotherapy-immunotherapy synergism will determine INGN-225's future role as an anticancer therapy.
authors.affiliation: Department of Thoracic Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. alberto.chiappori@moffitt.org
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Chiappori
authors.forename: Hatem
authors.initials: H
authors.lastname: Soliman
authors.forename: William E
authors.initials: WE
authors.lastname: Janssen
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D055752:Small Cell Lung Carcinoma / Q000276:immunology* / Q000628:therapy*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; C551395:INGN 225; D016159:Tumor Suppressor Protein p53