title: Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy.
abstract: Electroporation improves the anti-tumour efficacy of chemotherapeutic and gene therapies. Combining electroporation-mediated chemotherapeutics with interleukin 12 (IL-12) plasmid DNA produces a strong yet safe anti-tumour effect for treating primary and refractory tumours. A previously published report demonstrated the efficacy of a single cycle of IL-12 plasmid DNA and bleomycin in canines, and, similarly, this study further demonstrates the safety and efficacy of repeated cycles of chemotherapy plus IL-12 gene therapy for long-term management of aggressive tumours. Thirteen canine patients were enrolled in this study and received multiple cycles of electro-chemo-gene therapy (ECGT) with IL-12 pDNA and either bleomycin or gemcitabine. ECGT treatments are very effective for inducing tumour regression via an antitumour immune response in all tested histotypes except for sarcomas, and these treatments can quickly eradicate or debulk large squamous cell carcinomas. The versatility of ECGT allows for response-based modifications which can overcome treatment resistance for affecting refractory lesions. Importantly, not a single severe adverse event was noted even in animals receiving the highest doses of chemotherapeutics and IL12 pDNA over multiple treatment cycles. This report highlights the safety, efficacy and versatility of this treatment strategy. The data reveal the importance of inducing a strong anti-tumour response for successfully affecting not only the treated tumours, but also non-treated metastatic tumours. ECGT with IL12 pDNA plus chemotherapy is an effective strategy for treating multiple types of spontaneous cancers including large, refractory and multiple tumour burdens.
authors: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Jeffry
authors: J
authors: Cutrera
authors: Glenn
authors: G
authors: King
authors: Pamela
authors: P
authors: Jones
authors: Kristin
authors: K
authors: Kicenuik
authors: Elias
authors: E
authors: Gumpel
authors: Xueqing
authors: X
authors: Xia
authors: Shulin
authors: S
authors: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004285:Dogs; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D001761:Bleomycin; D018664:Interleukin-12; D000093542:Gemcitabine
keywords: cancer; chemotherapy; electroporation; immunotherapy; interleukin 12; personalized therapy
references: BMC Cancer. 2013;13:38
references: 23360213
references: Schweiz Arch Tierheilkd. 2011 Nov;153(11):509-13
references: 22045456
references: Cancer Discov. 2012 Mar;2(3):260-9
references: 22585996
references: J Clin Oncol. 2008 Dec 20;26(36):5896-903
references: 19029422
references: Anticancer Res. 2001 Jul-Aug;21(4A):2483-8
references: 11724311
references: Anticancer Res. 2005 Mar-Apr;25(2A):839-45
references: 15868917
references: Methods Mol Biol. 2008;423:319-25
references: 18370210
references: Radiol Oncol. 2013 Mar;47(1):32-41
references: 23450195
references: In Vivo. 2007 Sep-Oct;21(5):897-9
references: 18019432
references: J Vet Intern Med. 2011 Mar-Apr;25(2):407-11
references: 21382075
references: In Vivo. 2008 Jan-Feb;22(1):51-3
references: 18396782
references: Cytokine. 1998 Apr;10(4):241-8
references: 9617567
references: Curr Pharm Des. 2012;18(23):3406-15
references: 22663554
references: Ann Surg Oncol. 2009 Jan;16(1):191-9
references: 18987914
references: Clin Cancer Res. 2006 Jan 1;12(1):257-63
references: 16397050
references: J Mol Med (Berl). 2001;78(12):692-702
references: 11434722
references: Radiol Oncol. 2011 Mar;45(1):31-9
references: 22933932
references: Int J Cancer. 2009 Aug 1;125(3):698-707
references: 19431145
references: Clin Cancer Res. 2006 May 15;12(10):3177-83
references: 16707618
references: Cancer Gene Ther. 2000 Jul;7(7):1060-8
references: 10917209
references: J Cell Mol Med. 2013 Nov;17(11):1465-74
references: 24251770
references: Mol Ther. 2003 Nov;8(5):738-45
references: 14599806
references: Mol Ther. 2005 Nov;12(5):942-9
references: 15953768
references: Radiol Oncol. 2012 Dec;46(4):302-11
references: 23412658
references: Cancer Gene Ther. 2010 Jul;17(7):457-64
references: 20150931
references: Gene Ther. 2002 Jan;9(1):64-74
references: 11850724
references: Expert Opin Pharmacother. 2003 Dec;4(12):2151-63
references: 14640914
references: Semin Oncol. 2012 Apr;39(2):145-9
references: 22484186
references: J Immunother. 2011 Jan;34(1):58-64
references: 21150713
references: Oncoimmunology. 2013 Jun 1;2(6):e24499
references: 23894709
references: J Interferon Cytokine Res. 1997 Nov;17(11):713-8
references: 9402110
references: J Transl Med. 2012;10:234
references: 23171444
references: Science. 1995 Nov 10;270(5238):908
references: 7481785
references: J Exp Clin Cancer Res. 2008;27:58
references: 18980687
references: Clin Cancer Res. 2007 Aug 15;13(16):4677-85
references: 17699845
references: J Clin Oncol. 2011 May 1;29(13):e372-7
references: 21321291
references: Methods Mol Biol. 2014;1121:247-56
references: 24510829
references: Methods Mol Biol. 2014;1121:233-9
references: 24510827
references: Surgery. 2013 Sep;154(3):496-503
references: 23972655
references: Clin Cancer Res. 1997 Mar;3(3):409-17
references: 9815699
references: Med Biol Eng Comput. 2012 Dec;50(12):1213-25
references: 23179413
references: J Comp Pathol. 2009 Jul;141(1):17-26
references: 19362315
references: In Vivo. 2009 Jan-Feb;23(1):55-62
references: 19368125
references: Clin Cancer Res. 1998 May;4(5):1183-91
references: 9607576
references: Mol Ther. 2011 Aug;19(8):1468-77
references: 21386825