ALLOANTIGEN GENE-THERAPY FOR SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - RESULTS OF A PHASE-1 TRIAL

Objective: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign clas s I major histocompatibility complex protein in patients with head and neck cancer. Design: Phase 1 prospective clinical trial. Setting: Aca demic medical setting. Patients: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and d id not express HLA-B7, a class I major histocompatibility complex prot ein. Intervention: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-9 cont ains a plasmid complementary DNA complexed with a cationic lipid, whic h results in expression of HLA-B7. Main Outcome Measures: Patients wer e assessed for any toxic effects and for any change in tumor volume. B iopsy specimens obtained before and after therapy were evaluated by im munohistochemistry to detect HLA-B7 expression and with the terminal d eoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin n ick end labeling (TUNEL) assay to detect any induction of apoptosis. R esults: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for mo re than 17 months since commencing treatment, with no clinical evidenc e of disease but with persistent histological evidence of cancer. Anal ysis of the biopsy specimens from 2 of the patients who responded to t herapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated ex tensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. Conclusions: These data demonstra te the potential efficacy and lack of toxicity of this form of alloant igen gene therapy. A multi-institutional study has been initiated to e xpand on these findings.