1. Immunological, anti-angiogenic and clinical effects of intratumoral interleukin 12 electrogene therapy combined with metronomic cyclophosphamide in dogs with spontaneous cancer: A pilot study.
- Author
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Cicchelero L, Denies S, Vanderperren K, Stock E, Van Brantegem L, de Rooster H, and Sanders NN
- Subjects
- Administration, Metronomic veterinary, Animals, Chemotherapy, Adjuvant veterinary, Dog Diseases genetics, Dog Diseases immunology, Dog Diseases metabolism, Dogs, Humans, Interferon-gamma metabolism, Interleukin-12 immunology, Lymphocytes, Tumor-Infiltrating drug effects, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Neoplasms genetics, Neoplasms immunology, Neoplasms therapy, Neovascularization, Pathologic, Pilot Projects, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Thrombospondin 1 metabolism, Time Factors, Tumor Microenvironment, Vascular Endothelial Growth Factor A metabolism, Antineoplastic Agents, Alkylating administration & dosage, Cyclophosphamide administration & dosage, Dog Diseases therapy, Genetic Therapy veterinary, Immunotherapy veterinary, Interleukin-12 genetics, Neoplasms veterinary
- Abstract
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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2017
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