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.

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.

• Authors: L L Gleich, J L Gluckman, J Nemunaitis, J Y Suen, E Hanna, G T Wolf, M D Coltrera, D B Villaret, L Wagman, D Castro, M Gapany, W Carroll, D Gillespie, L M Selk
• Journal: Archives of otolaryngology--head & neck surgery (Arch Otolaryngol Head Neck Surg) Vol. 127 Issue 7 Pg. 775-9 (Jul 2001) ISSN: 0886-4470 [Print] United States
• PMID: 11448348 (Publication Type: Journal Article)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (mortality, pathology, therapy)
• DNA (administration & dosage, 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, therapeutic use)
• Humans
• Immunotherapy
• Injections, Intralesional
• Lipids (adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Staging
• Otorhinolaryngologic Neoplasms (mortality, pathology, therapy)
• Plasmids (adverse effects, genetics, therapeutic use)
• Survival Rate