Clinical evaluation of adenoviral-mediated p53 gene transfer: review of INGN 201 studies.
Gene therapy represents a new modality of cancer therapeutics based on novel mechanisms of action. Modified adenoviruses have important properties that lend themselves readily to commercial-scale manufacturing; with an excellent safety record, they have been used as the gene transfer vector in most clinical studies to date. They provide a potent means of delivering genes into cancer cells. Although multiple genes are involved in the development of malignancy, preclinical models (and now clinical studies) have proven that insertion of a single gene, p53, can arrest cancer cell growth and induce apoptosis and tumor regression in advanced cancers such as squamous cell cancer of the head and neck and non-small cell lung cancer. With equally strong rationale, clinical studies using combination approaches also have been initiated, with promising results in localized inoperable non-small cell lung cancer. In addition, the apparent safety, and especially the lack of adverse effects on normal tissues at injection sites following gene transfer, have stimulated an evaluation of intervention in the postoperative surgical adjuvant setting and in treating premalignancies. The goal of these studies has been to provide an antitumor locoregional effect. This may result in effective palliation in the advanced-disease setting, especially for diseases that do not metastasize widely. However, the most exciting near-term potential of p53 gene transfer using INGN 201 will be in up-front regimens in combination with surgery, radiation, and chemotherapy in the many clinical settings where local disease control remains suboptimal.
Merritt
J A
JA
Introgen Therapeutics, Inc, Houston, TX 77004, USA.
Roth
J A
JA
Logothetis
C J
CJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes