Abstract
This chapter reviews the requisite steps in a translational cancer gene therapy trial. As with all clinical trials, translational cancer gene therapy trials require clear concise objectives and endpoints. Several unique factors exist with gene therapy trials that must be considered prior to trial development, including the type of vector desired, the delivery mechanism and the different gene therapy strategies required for gene product expression. Progression of cancer gene therapy trials from the preclinical phase to the post approval phase IV stage require a careful strategy to meet the strict regulatory requirements at both the federal and local institutional level. Safety monitoring is especially important with gene therapy trials because of the high visibility of gene therapy trials and the impact on the trial, patient, and the gene therapy field in general if adverse events occur. Financial considerations should be addressed at the outset because of the increased costs associated with a translational gene therapy trial.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans—immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990;323:570–578.
Edelstein ML, Abedi MR, Wixon J, et al. Gene therapy clinical trials worldwide 1989–2004-an overview J Gene Med 2004;6:597–602.
Swisher SG, Roth JA. Gene therapy for human lung cancers. Surg Oncol Clin N Am 1998;7:603–616.
Jia W, Zhou Q. Viral vectors for cancer gene therapy: viral dissemination and tumor targeting Curr Gene Ther 2005;5:133–142
Glover DJ, Lipps HJ, Jans DA. Towards safe, non-viral therapeutic gene expression in humans Nat Rev Genet 2005;6:299–310
Trent RJ, Alexander IE. Gene therapy: applications and progress towards the clinic. Intern Med J 2004;34:621–625.
Swisher SG, Roth JA, Komaki R, et al. Induction of p53 regulated genes and tumor regression in lung cancer following intratumoral delivery of adenoviral p53 (RPR/INGN 201) and radiation therapy. Clin Cancer Res 2003;9:93–101.
Margolin KA, Rayner AA, Hawkins MJ, et al. Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines J Clin Oncol 1989;7:486–498.
Sangro B, Mazzolini G, Ruiz J, et al. Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors J Clin Oncol 2004;22:1389–1397.
Belldegrun A, Tso CL, Zisman A, et al. Interleukin 2 gene therapy for prostate cancer: phase I clinical trial and basic biology Hum Gene Ther 2001;12:883–892.
Ren HBT, Soling A, Warnke PC, et al. Immunogene therapy of recurrent gliobastoma multiforme with a liposomally encapsulated replication-incompenent semliki forest virus vector carrying the human interleukin-12 gene-A pahe I/II clinical protocl. J Neuro-Oncol 2003;64:147–154.
Zajac P, Oertli D, Marti W, et al. Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients Hum Gene Ther 2003;14:1497–1510.
Lang FF, Bruner JM, Fuller GN, et al. Phase I trail of adenovirus-mediated p53 gene therapy for recurrent giloma: biological and clinical results. J Clin Oncol 2003;21:2508–2518.
Hughes RM. Strategies for cancer gene therapy. J Surg Oncol 2004;85:28–35.
Tolcher AW. Preliminary phase I results of G3139 (bcl-2 antisense oligonucleotide) therapy in combination with docetaxel in hormone-refractory prostate cancer. Semin Oncol 2001;28:67–70.
Lopes de Menezes DE, Mayer LD. Pharmacokinetics of Bcl-2 antisense oligonucleotide (G3139) combined with doxorubicin in SCID mice bearing human breast cancer solid tumor xenografts. Cancer Chemother Pharmacol 2002;49:57–68
Dummer R, Bergh J, Karlsson Y, et al. Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors. Cancer Gene Ther 2000;7:1069–1076.
Roth JA, Cristiano RJ. Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997;89:21–39.
Pearson AS, Spitz FR, Swisher SG, et al. Up-regulation of the proapoptotic mediators Bax and Bak after adenovirus-mediated p53 gene transfer in lung cancer cells. Clin Cancer Res 2000;6:887–890.
Kagawa S, Gu J, Swisher SG, et al. Antitumor effect of adenovirus-mediated Bax gene transfer on p55-sensitive and p53-resistant cancer lines. Cancer Res 2000;60:1157–1161.
Pataer A, Fang B, Yu R, et al. Adenoviral bak overexpression mediates caspase-dependent tumor killing. Cancer Res 2000;60:788–792.
Kountouras J, Zavos C, and Chatzopoulos D. Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies. J Surg Oncol 2005;90:249–259.
Lowe SW, Ruley HE, Jacks T, et al. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993;74:957–967
Nguyen DM, Spitz FR, Yen N, et al. Gene therapy for lung cancer: enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer. J Thorac Cardiovasc Surg 1996;112:1372–1377.
Pilaro AM, Serabian MA. Preclinical development strategies for novel gene therapeutic products. Toxicol Pathol 1999;27:4–7.
Aguilar LK, Aguilar-Cordova E. Evolution of a gene therapy clinical trial. From bench to bedside and back. J Neurooncol 2003;65:307–315.
Manilla P, Rebello T, Afable C, et al. Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector. Hum Gene Ther 2005; 16:17–25.
Miller AE, Simek SL. Regulatory aspects of gene therapy. 2005;371–382.
Amin S, Robins RA, Maxwell-Armstrong CA, et al. Vaccine-induced apoptosis: a novel clinical trial end point? Cancer Res 2000;60:3132–3136.
Schuler M, Herrmann R, De Greve JL, et al. Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study. J Clin Oncol 2001;19:1750–1758.
Parulekar WR, Eisenhauer EA. Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents: theory and practice Journal of the National Cancer Institute 2004;96:990–997.
Tan AR, Swain SM. Novel agents: clinical trial design. Semin Oncol 2001;28:148–153.
Teh BS, Ayala G, Aguilar L, et al. Phase I–II trial evaluating combined intensity-modulated radiotherapy and in situ gene therapy with or without hormonal therapy in treatment of prostate cancer-interim report on PSA response and biopsy data. Int J Rad Oncol Biol Phys 004;58:1520–1529.
Anderson BD, Adamson PC, Weiner SL, et al. Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives J Clin Oncol 2004;22:4846–4850.
NIH Guidelines for research involving recombinant DNA molecules (NIH Guidelines). NIH 2002.
Lichtenstein DL, Wold WS Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission. Cancer Gene Ther 2004; 11:819–829.
Lehrman S. Virus treatment questioned after gene therapy death. Nature 1999;401:517–518.
Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003;302:415–419.
Hacein-Bey-Abina S, Le Deist F, Carlier F, et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 2002;346:1185–1193.
Mehl B, Santell J. Projecting future drug expenditures—2001. Am J Health Syst Pharm 2001;58: 125–133.
Danzon P, Towse A. The economics of gene therapy and of pharmacogenetics Value Health 2002;5:5–13.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
von Holzen, U.W., Swisher, S.G. (2007). Steps in a Translational Cancer Gene Therapy Trial. In: Hunt, K.K., Vorburger, S.A., Swisher, S.G. (eds) Gene Therapy for Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-222-9_25
Download citation
DOI: https://doi.org/10.1007/978-1-59745-222-9_25
Publisher Name: Humana Press
Print ISBN: 978-1-58829-472-2
Online ISBN: 978-1-59745-222-9
eBook Packages: MedicineMedicine (R0)