title: Intralesional lipid-complexed cytokine/superantigen immunogene therapy for spontaneous canine tumors.
abstract: These studies sought to determine the gene expression and short-term effects of intralesional lipid-complexed immunogene therapy with constructs encoding Staphylococcus aureus enterotoxin A and canine interleukin-2 (L-SEA/cIL-2) in dogs with tumors of various histotypes, and then to assess the safety and efficacy of repeated L-SEA/cIL-2 injections in dogs with spontaneous soft tissue sarcomas (STS). In the first study, pet dogs with a variety of tumors received a single intralesional injection of L-SEA/cIL-2, and surgical excision was performed 48 h later. In the second study, dogs with histologically confirmed STS were treated weekly for a maximum of 12 weeks with escalating doses of L-SEA/cIL-2. Tumors were then surgically excised and assessed histologically and immunohistochemically. Overall, treatments were well tolerated, with no dose-limiting toxicities encountered. At 48 h, in the single injection study, plasmid DNA was detected in 14 of 16 tumor samples, and plasmid-specific mRNA was detected in 3 of 14. In the multiple injection study, the overall response rate in dogs with STS was 25%, consisting of 3 complete responses (CR) and 1 partial response (PR). Diffuse lymphoplasmacytic inflammation was observed in all tumors from patients experiencing CR or PR, whereas these changes were not evident in tumors from nonresponders. The infiltrate was composed primarily of CD3(+) cells at 48 h from the single-injection study, and was composed of both CD3(+) and CD79a(+) cells at 12 weeks in responding dogs from the multiple-injection study. In conclusion, these studies suggests that intralesional L-SEA/cIL-2 immunotherapy is well tolerated, results in detectable transgene expression in canine tumors, and has antitumor activity in dogs with spontaneous STS.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, WI 53706, Madison, USA. thammd@svm.vetmed.wisc.edu
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Thamm
authors.forename: Ilene D
authors.initials: ID
authors.lastname: Kurzman
authors.forename: E Gregory
authors.initials: EG
authors.lastname: Macewen
authors.forename: Rhonda
authors.initials: R
authors.lastname: Feinmehl
authors.forename: Todd L
authors.initials: TL
authors.lastname: Towell
authors.forename: Susan L
authors.initials: SL
authors.lastname: Longhofer
authors.forename: Christine M
authors.initials: CM
authors.lastname: Johnson
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Geoly
authors.forename: Dan T
authors.initials: DT
authors.lastname: Stinchcomb
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D004768:Enterotoxins / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D007167:Immunotherapy; D015552:Injections, Intralesional; D007376:Interleukin-2 / Q000235:genetics*; D050356:Lipid Metabolism; D008297:Male; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000235:genetics; D018089:Superantigens / Q000235:genetics; D014162:Transfection
chemical_list: D004768:Enterotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal