Head and neck cancer: gene therapy approaches. Part II: genes delivered.
In Part I, the review summarised the safety of adenoviral vectors and provided insight into approaches being undertaken to improve the specificity, durability and potency of adenoviral delivery vehicles. In Part II, brief discussions are held regarding results of preclinical and clinical trials with a variety of different genes, which have demonstrated antitumour activity in squamous cell carcinoma of the head and neck region (HNSCC). Studies have been performed with a variety of immune modulatory genes. Preliminary results demonstrate activity with several cytokine genes, tumour antigen genes and co-stimulatory molecule genes. Despite only preliminary results, thus far, a theoretical attractive feature for the use of gene therapy for the enhancement of immune modulation is that local injection of the gene product appears to be well tolerated. It is also successful in inducing systemic immune response, potentially providing effect to metastatic sites distal from the injected site. Animal studies have confirmed efficacy in the use of specific targeting of molecules regulating cancer growth (EGF receptor [EGFR], super oxide dismutase [SOD], cyclin D1, E1A and Bcl-2). These approaches are discussed. However, the most significant clinical advances for the use of gene therapy in advanced HNSCC involves two agents: Adp53 and ONYX-015. Preliminary Phase I and II results suggest evidence of efficacy and justify accrual Phase III trials, which are currently ongoing.
Nemunaitis
John
J
3535 Worth Street, Collins Building, 5th Floor, Dallas, Texas 75246, USA. John.Nemunaitis@USOncology.com
O'Brien
John
J
D000256:Adenoviridae; D017500:Adenovirus E1A Proteins / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005804:Genes, Lethal; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D015316:Genetic Therapy; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D013482:Superoxide Dismutase / Q000235:genetics; D014765:Viral Vaccines / Q000627:therapeutic use
D017500:Adenovirus E1A Proteins; D000276:Adjuvants, Immunologic; D016207:Cytokines; D014765:Viral Vaccines; C464532:dl1520; D013482:Superoxide Dismutase; D066246:ErbB Receptors