Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E. Campus Dr, Columbia, MO, 65203, USA.
Comparative Oncology Radiobiology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E. Campus Dr, Columbia, MO, 65203, USA.
Vet Res. 2018 Apr 24;49(1):38. doi: 10.1186/s13567-018-0531-0.
Clostridium novyi-NT (CVN-NT) spores germinate in hypoxic regions of tumors and have successfully cured induced neoplasia in mouse models and resulted in objective tumor responses in naturally developing neoplasia in the dog. The objective of this pilot, descriptive, prospective, clinical investigation, was to evaluate and describe the immune response to CNV-NT spores to better understand which immune pathways might play a role in the response to this bacteriolytic immunotherapy. Intratumoral injection of CNV-NT spores result in increased phagocytosis and NK cell-like function after treatment. Intravenous injection of CNV-NT spores resulted in increased LPS-induced TNF-α production, LTA-induced IL-10 production and NK cell-like function post-treatment. Increased NK cell-like function was sustained to 28 (intratumoral) or 56 (intravenous) days post-treatment, and increased phagocytic function was sustained to 28 days post-treatment suggesting that CNV-NT spores induce longer-term immune cell function changes. Future investigations evaluating long-term immune system changes and associations between immune function and tumor remission rates should include evaluation of these pathways.
新型努氏梭菌（CVN-NT）孢子在肿瘤缺氧区域发芽，并已成功治愈了小鼠模型中的诱导性肿瘤，且在犬自然发生的肿瘤中引起了客观的肿瘤反应。本试验为描述性、前瞻性、临床研究，旨在评估和描述对 CVN-NT 孢子的免疫反应，以更好地了解哪些免疫途径可能在对这种溶菌素免疫疗法的反应中发挥作用。瘤内注射 CVN-NT 孢子后，治疗后吞噬作用和 NK 样细胞功能增加。静脉注射 CVN-NT 孢子后，LPS 诱导的 TNF-α产生、LTA 诱导的 IL-10 产生和 NK 样细胞功能增加。NK 样细胞功能可持续至治疗后 28 天（瘤内）或 56 天（静脉内），吞噬功能可持续至治疗后 28 天，表明 CVN-NT 孢子诱导更长期的免疫细胞功能变化。未来评估长期免疫系统变化以及免疫功能与肿瘤缓解率之间的关系的研究应包括对这些途径的评估。
