Gene Therapy Used in Cancer Treatment

Biomedicines - Tập 2 Số 2 - Trang 149-162
Thomas Wirth1, Seppo Ylä‐Herttuala2,3
1Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland. [email protected].
2Research Unit and Gene Therapy Unit, Kuopio University Hospital, 70210 Kuopio, Finland. [email protected].
3Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland. [email protected].

Tóm tắt

Cancer has been, from the beginning, a target of intense research for gene therapy approaches. Currently, more than 60% of all on-going clinical gene therapy trials worldwide are targeting cancer. Indeed, there is a clear unmet medical need for novel therapies. This is further urged by the fact that current conventional cancer therapies are frequently troubled by their toxicities. Different gene therapy strategies have been employed for cancer, such as pro-drug activating suicide gene therapy, anti-angiogenic gene therapy, oncolytic virotherapy, gene therapy-based immune modulation, correction/compensation of gene defects, genetic manipulation of apoptotic and tumor invasion pathways, antisense, and RNAi strategies. Cancer types, which have been targeted with gene therapy, include brain, lung, breast, pancreatic, liver, colorectal, prostate, bladder, head and neck, skin, ovarian, and renal cancer. Currently, two cancer gene therapy products have received market approval, both of which are in China. In addition, the stimulation of the host’s immune system, using gene therapeutic approaches, has gained vast interest. The intention of this review is to point out the most commonly viral and non-viral vectors and methods used in cancer gene therapy, as well as highlight some key results achieved in clinical trials.

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Tài liệu tham khảo

Hanahan, 2000, The hallmarks of cancer, Cell, 100, 57, 10.1016/S0092-8674(00)81683-9

Bissell, 2011, Why donʼt we get more cancer? A proposed role of the microenvironment in restraining cancer progression, Nat. Med., 17, 320, 10.1038/nm.2328

Rogers, 1968, Use of viruses as carriers of added genetic information, Nature, 219, 749, 10.1038/219749a0

Rogers, 1973, Induction of arginase activity with the Shope papilloma virus in tissue culture cells from an argininemic patient, J. Exp. Med., 137, 1091, 10.1084/jem.137.4.1091

Terheggen, 1975, Unsuccessful trial of gene replacement in arginase deficiency, Z. Kinderheilkd., 119, 1

Rosenberg, 1990, Gene transfer into humans—Immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction, N. Engl. J. Med., 323, 570, 10.1056/NEJM199008303230904

MacMillan, 1982, The Cline affair, Nurs. Times, 78, 383

Beutler, 2001, The Cline affair, Mol. Ther., 4, 396, 10.1006/mthe.2001.0486

Raty, 2008, Improving safety of gene therapy, Curr. Drug Saf., 3, 46, 10.2174/157488608783333925

Coughlan, 2010, Tropism-modification strategies for targeted gene delivery using adenoviral vectors, Viruses, 2, 2290, 10.3390/v2102290

Montini, 2011, Quest for safety at AAValon, Blood, 117, 3249, 10.1182/blood-2011-02-321984

Biffi, 2011, Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection, Blood, 117, 5332, 10.1182/blood-2010-09-306761

Matrai, 2010, Recent advances in lentiviral vector development and applications, Mol. Ther., 18, 477, 10.1038/mt.2009.319

Sharma, 2009, Adenovirus receptors and their implications in gene delivery, Virus Res., 143, 184, 10.1016/j.virusres.2009.02.010

Heyde, 2007, Gene therapy used for tissue engineering applications, J. Pharm. Pharmacol., 59, 329, 10.1211/jpp.59.3.0002

Pathak, 2009, Recent trends in non-viral vector-mediated gene delivery, Biotechnol. J., 4, 1559, 10.1002/biot.200900161

Mudhakir, 2009, Learning from the viral journey: How to enter cells and how to overcome intracellular barriers to reach the nucleus, AAPS J., 11, 65, 10.1208/s12248-009-9080-9

Escoffre, 2010, Gene transfer: How can the biological barriers be overcome?, J. Membr. Biol., 236, 61, 10.1007/s00232-010-9275-0

Lang, 2003, Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: Biological and clinical results, J. Clin. Oncol., 21, 2508, 10.1200/JCO.2003.21.13.2508

Raty, 2008, Gene therapy: the first approved gene-based medicines, molecular mechanisms and clinical indications, Curr. Mol. Pharmacol., 1, 13, 10.2174/1874467210801010013

Han, 2003, Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: Phase I clinical trial and follow up, Zhonghua Yi Xue Za Zhi, 83, 2029

Peng, 2005, Current status of gendicine in China: Recombinant human Ad-p53 agent for treatment of cancers, Hum. Gene Ther., 16, 1016, 10.1089/hum.2005.16.1016

Bischoff, 1996, An adenovirus mutant that replicates selectively in p53-deficient human tumor cells, Science, 274, 373, 10.1126/science.274.5286.373

Chiocca, 2004, A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting, Mol. Ther., 10, 958, 10.1016/j.ymthe.2004.07.021

Yu, 2007, Clinical trials with oncolytic adenovirus in China, Curr. Cancer. Drug Targets, 7, 141, 10.2174/156800907780058817

Hu, 2006, A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor, Clin. Cancer Res., 12, 6737, 10.1158/1078-0432.CCR-06-0759

Harrington, 2010, Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck, Clin. Cancer Res., 16, 4005, 10.1158/1078-0432.CCR-10-0196

Kershaw, 2013, Gene-engineered T cells for cancer therapy, Nat. Rev. Cancer, 13, 525, 10.1038/nrc3565

Morgan, 2006, Cancer regression in patients after transfer of genetically engineered lymphocytes, Science, 314, 126, 10.1126/science.1129003

Robbins, 2011, Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1, J. Clin. Oncol., 29, 917, 10.1200/JCO.2010.32.2537

Kochenderfer, 2013, Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors, Nat. Rev. Clin. Oncol., 10, 267, 10.1038/nrclinonc.2013.46

Kochenderfer, 2012, B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells, Blood, 119, 2709, 10.1182/blood-2011-10-384388

Herman, 2013, Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: Final results, J. Clin. Oncol., 31, 886, 10.1200/JCO.2012.44.7516

Malmstrom, 2010, AdCD40L immunogene therapy for bladder carcinoma—The first phase I/IIa trial, Clin. Cancer Res., 16, 3279, 10.1158/1078-0432.CCR-10-0385

Chiocca, 2008, A phase I trial of Ad.hIFN-beta gene therapy for glioma, Mol. Ther., 16, 618, 10.1038/sj.mt.6300396

Freeman, 1993, The “bystander effect”: Tumor regression when a fraction of the tumor mass is genetically modified, Cancer Res., 53, 5274

Sandmair, 2000, Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses, Hum. Gene Ther., 11, 2197, 10.1089/104303400750035726

Eck, 1996, Treatment of advanced CNS malignancies with the recombinant adenovirus H5.010RSVTK: a phase I trial, Hum. Gene Ther., 7, 1465, 10.1089/hum.1996.7.12-1465

Rainov, 2000, A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme, Hum. Gene Ther., 11, 2389, 10.1089/104303400750038499

Immonen, 2004, AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: A randomised, controlled study, Mol. Ther., 10, 967, 10.1016/j.ymthe.2004.08.002

Westphal, M., Yla-Herttuala, S., Martin, J.F., Warnke, P., Menei, P., Eckland, D., Kinley, J., Kay, R., and Ram, Z. (2013). Adenovirus-mediated gene therapy with stimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): A randomised, open-label, phase 3 trial. Lancet Oncol., in press.

Thoma, 2013, Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy, Virology, 447, 74, 10.1016/j.virol.2013.08.032

Wirth, 2006, Safety profile of plasmid/liposomes and virus vectors in clinical gene therapy, Curr. Drug Saf., 1, 253, 10.2174/157488606777934440

Wang, 2011, The next step in gene delivery: Molecular engineering of adeno-associated virus serotypes, J. Mol. Cell. Cardiol., 50, 793, 10.1016/j.yjmcc.2010.10.017

Kim, 2011, A new generation of serotype chimeric infectivity-enhanced conditionally replicative adenovirals: The safety profile of ad5/3-Delta24 in advance of a phase I clinical trial in ovarian cancer patients, Hum. Gene Ther., 22, 821, 10.1089/hum.2010.180

Wang, 2011, Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors, Hum. Gene Ther., 22, 1389, 10.1089/hum.2011.031

Barnett, 2002, Targeted adenoviral vectors, Biochim. Biophys. Acta, 1575, 1, 10.1016/S0167-4781(02)00249-X

Cronin, 2005, Altering the tropism of lentiviral vectors through pseudotyping, Curr. Gene Ther., 5, 387, 10.2174/1566523054546224

Kim, 2009, Hypoxia-specific gene expression for ischemic disease gene therapy, Adv. Drug Deliv. Rev., 61, 614, 10.1016/j.addr.2009.04.009

Harvey, 2011, Adenovirus-mediated hypoxia-targeted gene therapy using HSV thymidine kinase and bacterial nitroreductase prodrug-activating genes in vitro and in vivo, Cancer Gene Ther., 18, 773, 10.1038/cgt.2011.43

Urnov, 2010, Genome editing with engineered zinc finger nucleases, Nat. Rev. Genet., 11, 636, 10.1038/nrg2842

Staunstrup, 2009, Hybrid lentivirus-transposon vectors with a random integration profile in human cells, Mol. Ther., 17, 1205, 10.1038/mt.2009.10

Mates, 2009, Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates, Nat. Genet., 41, 753, 10.1038/ng.343

VandenDriessche, 2009, Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cells, Blood, 114, 1461, 10.1182/blood-2009-04-210427

Patel, 2000, Radiation-induced sarcoma, Curr. Treat. Options Oncol., 1, 258, 10.1007/s11864-000-0037-6

Harris, 1976, The carcinogenicity of anticancer drugs: A hazard in man, Cancer, 37, 1014, 10.1002/1097-0142(197602)37:2+<1014::AID-CNCR2820370805>3.0.CO;2-Z

Boffetta, 1994, Secondary malignancies following cancer chemotherapy, Acta Oncol., 33, 591, 10.3109/02841869409121767

Alba, 2005, Gutless adenovirus: Last-generation adenovirus for gene therapy, Gene Ther., 12, S18, 10.1038/sj.gt.3302612