Immunological, anti-angiogenic and clinical effects of intratumoral interleukin 12 electrogene therapy combined with metronomic cyclophosphamide in dogs with spontaneous cancer: A pilot study.
The immunological, anti-angiogenic and clinical effects of metronomic cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT coincided with erythema and swelling of the tumor. In the tumor, a transient increase in IL-12 levels was measured, whereas a continuous increase in interferon γ (IFNγ) and thrombospondin 1 (TSP-1) were determined in contrast to a continuous decrease in vascular endothelial growth factor (VEGF). In the serum, a transient increase in IL-12 and IL-10 levels were noted in contrast to a transient decrease in VEGF and TSP-1. The treatment resulted in a significant anti-angiogenic effect. Although all primary tumors continued to progress in time, this progression was slower than before treatment according to the contrast-enhanced ultrasound data. Besides the encouraging immunostimulatory and anti-angiogenic effects observed in all dogs we also noticed in 4 out of 6 dogs clinically relevant improvements in quality of life and weight. These results hold great promise for combinatorial strategies of IL-12 EGT and metronomic chemotherapy with conventional antitumor (immuno)therapies.
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, B-9820 Merelbeke, Belgium.
Laetitia
L
Cicchelero
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, B-9820 Merelbeke, Belgium.
Sofie
S
Denies
Department of Medical Imaging of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
Katrien
K
Vanderperren
Department of Medical Imaging of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
Emmelie
E
Stock
Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
Leen
L
Van Brantegem
Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University, Belgium. Electronic address: hilde.derooster@ugent.be.
Hilde
H
de Rooster
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, B-9820 Merelbeke, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University, Belgium. Electronic address: Niek.Sanders@ugent.be.
Niek N
NN
Sanders
D059250:Administration, Metronomic / Q000662:veterinary; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant / Q000662:veterinary; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004283:Dog Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004285:Dogs; D015316:Genetic Therapy / Q000662:veterinary*; D006801:Humans; D007167:Immunotherapy / Q000662:veterinary*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D009389:Neovascularization, Pathologic; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D013997:Time Factors; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D018664:Interleukin-12; D007371:Interferon-gamma; D003520:Cyclophosphamide
Angiogenesis; Contrast-enhanced ultrasound; Gene transfer; Immune stimulation; Interleukin 12; Metronomic cyclophosphamide