Gene therapy for head and neck cancer

Objectives/Hypothesis: New treatment methods are needed for head and neck c ancer to improve survival without increasing morbidity. Gene therapy is a p otential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology an d treatment strategies. Given the current technological vector Limitations in transmitting the therapeutic genes, treatments that require the fewest n umber of cells to be altered by the new gene are optimal. Therefore an immu ne-based gene therapy strategy was selected in which the tumors were transf ected with the gene for an alloantigen, human leukocyte antigen (HLA)-B7, a class I major histocompatibility complex (MHC). This would restore an anti gen presentation mechanism in the tumor to induce an antitumor response. Th is gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design: Prospective trial. Methods: Twenty pat ients with advanced head and neck cancer who had failed conventional therap y and did not express HLA-B7 were treated with gene therapy using a Lipid v ector by direct intratumoral injection. The gene therapy product contained the HLA-B7 gene and the PS-microglobulin gene, which permits complete expre ssion of the class I MHC at the cell surface. Patients were assessed for an y adverse effects, for changes in tumor size, for time to disease progressi on, and for survival. Biopsy specimens were assessed for pathological respo nse, HLA-B7 expression, apoptosis, cellular proliferation, CD-8 cells, gran zyme, and p53 status. Results: There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a part ial response and two patients had stable disease. Two of the tumors complet ely responded clinically, but tumor was still seen on pathological examinat ion. The time to disease progression in the responding patients was 20 to 8 0 weeks. The median survival in patients who completed gene therapy was 54: weeks, compared with 21 weeks in patients whose tumors progressed after th e first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA-B7 was demonstrated in the treated tumors, and incr eased apoptosis was seen in the responding tumors. Conclusion: Significant advances have been made in the field of gene therapy for cancer. Alloantige n gene therapy has had efficacy in the treatment of cancer and can induce t umor responses in head and neck tumors. Alloantigen gene therapy has signif icant potential as an adjunctive treatment of head and neck cancer.