Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous cell carcinoma of the head and neck

Arch Otolaryngol Head Neck Surg. 2001 Jul;127(7):775-9.

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.

Design: Multi-institutional prospective trial.

Setting: Academic medical setting.

Patients: 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.

Intervention: 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.

Main outcome measures: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • DNA / administration & dosage*
  • DNA / adverse effects
  • DNA, Recombinant
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Gene Transfer Techniques*
  • HLA-B7 Antigen / adverse effects
  • HLA-B7 Antigen / therapeutic use*
  • Humans
  • Immunotherapy*
  • Injections, Intralesional
  • Lipids / adverse effects
  • Lipids / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Otorhinolaryngologic Neoplasms / mortality
  • Otorhinolaryngologic Neoplasms / pathology
  • Otorhinolaryngologic Neoplasms / therapy*
  • Plasmids / adverse effects
  • Plasmids / genetics*
  • Plasmids / therapeutic use*
  • Survival Rate

Substances

  • Allovectin-7
  • DNA, Recombinant
  • HLA-B7 Antigen
  • Lipids
  • DNA