Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous cell carcinoma of the head and neck.
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.
Gleich
L L
LL
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
Gluckman
J L
JL
Nemunaitis
J
J
Suen
J Y
JY
Hanna
E
E
Wolf
G T
GT
Coltrera
M D
MD
Villaret
D B
DB
Wagman
L
L
Castro
D
D
Gapany
M
M
Carroll
W
W
Gillespie
D
D
Selk
L M
LM
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
C096492:Allovectin-7; D004274:DNA, Recombinant; D015793:HLA-B7 Antigen; D008055:Lipids; D004247:DNA