title: Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  To investigate the safety and efficacy of alloantigen plasmid DNA therapy in patients with advanced head and neck squamous cell carcinoma using Allovectin-7 (Vical Inc, San Diego, Calif), a DNA/lipid complex designed to express the class I major histocompatibility complex antigen HLA-B7.
  
  
  METHODS
  Multi-institutional prospective trial.
  
  
  METHODS
  Academic medical setting.
  
  
  METHODS
  A total of 69 patients were enrolled in 3 sequential clinical trials: a single-center phase 1 trial and 2 multicenter phase 2 trials. Eligibility criteria included unresectable squamous cell carcinoma that failed conventional therapy, Karnofsky performance status score of 70 or greater, and no concurrent anticancer or immunosuppressive therapies.
  
  
  METHODS
  Patients received 2 biweekly intratumoral injections of 10 microg (phase 1 and first phase 2 trials) or 100 microg (second phase 2 trial) of Allovectin-7 followed by 4 weeks of observation. Patients with stable or responding disease after the observation period were given a second treatment cycle identical to the first.
  
  
  METHODS
  Patients were assessed for toxic effects, and tumor size was measured after cycles 1 (at 6 weeks) and 2 (at 16 weeks).
  
  
  RESULTS
  Allovectin-7 treatment was well tolerated, with no grade 3 or 4 drug-related toxic effects. Of 69 patients treated, 23 (33%) had stable disease or a partial response after the first cycle of treatment and proceeded to the second cycle. After the second cycle, 6 patients had stable disease, 4 had a partial response, and 1 had a complete response. Responses persisted for 21 to 106 weeks.
  
  
  CONCLUSIONS
  Intratumoral plasmid DNA immunotherapy for head and neck cancer with Allovectin-7 is safe, and further investigations are planned in patients with less advanced disease, where it could potentially improve patient survival and reduce the need for radical high-morbidity treatments.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati Medical Center, PO Box 670528, 213 Bethesda Ave, Cincinnati, OH 45267-0528, USA. lyon.gleich@uc.edu
authors.forename: L L
authors.initials: LL
authors.lastname: Gleich
authors.forename: J L
authors.initials: JL
authors.lastname: Gluckman
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: J Y
authors.initials: JY
authors.lastname: Suen
authors.forename: E
authors.initials: E
authors.lastname: Hanna
authors.forename: G T
authors.initials: GT
authors.lastname: Wolf
authors.forename: M D
authors.initials: MD
authors.lastname: Coltrera
authors.forename: D B
authors.initials: DB
authors.lastname: Villaret
authors.forename: L
authors.initials: L
authors.lastname: Wagman
authors.forename: D
authors.initials: D
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: Gapany
authors.forename: W
authors.initials: W
authors.lastname: Carroll
authors.forename: D
authors.initials: D
authors.lastname: Gillespie
authors.forename: L M
authors.initials: LM
authors.lastname: Selk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage* / Q000009:adverse effects; D004274:DNA, Recombinant; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015793:HLA-B7 Antigen / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D015552:Injections, Intralesional; D008055:Lipids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010039:Otorhinolaryngologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: C096492:Allovectin-7; D004274:DNA, Recombinant; D015793:HLA-B7 Antigen; D008055:Lipids; D004247:DNA