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Identification of immunologic and clinical characteristics that predict inflammatory response to C. Novyi-NT
Amy E DeClue1, Sandra M Axiak-Bechtel2, Yan Zhang3
1Department of Veterinary Medicine and Surgery, Comparative Internal Medicine Laboratory, University of Missouri, College of Veterinary Medicine, 900 E. Campus Dr, Columbia, MO, 65203, USA. decluea@misssouri.edu.
Background:
Clostridium novyi-NT (CNV-NT), has shown promise as a bacterolytic therapy for solid tumors in mouse models and in dogs with naturally developing neoplasia. Factors that impact the immunologic response to therapy are largely unknown. The goal of this pilot study was to determine if plasma immune biomarkers, immune cell function, peripheral blood cytological composition and tumor characteristics including evaluation of a PET imaging surrogate of tumor tissue hypoxia could predict which dogs with naturally developing naïve neoplasia would develop an inflammatory response to CNV-NT.
Results:
Dogs that developed an inflammatory response to CNV-NT had a higher heart rate, larger gross tumor volume, greater tumor [64Cu]ATSM SUVMax, increased constitutive leukocyte IL-10 production, more robust NK cell-like function and greater peripheral blood lymphocyte counts compared to dogs that did not develop an inflammatory response to CNV-NT. Of these, unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume appeared to be the best predictors of which dogs will develop an inflammatory response to CNV-NT.
Conclusions:
Development of inflammation in response to CNV-NT is best predicted by pretreatment unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume.
Insights
Clostridium novyi-NT (CNV-NT) therapy for tumors in dogs can cause inflammation. Pretreatment IL-10 levels, heart rate, and tumor size predict this immune response, aiding treatment planning.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Clostridium novyi-NT (CNV-NT) shows potential as a bacterolytic therapy for solid tumors.
- Factors influencing the immune response to CNV-NT therapy are not well understood.
- This pilot study investigated predictors of inflammatory response in dogs receiving CNV-NT therapy.
Purpose of the Study:
- To identify immune biomarkers, cell function, and tumor characteristics that predict inflammatory response to CNV-NT.
- To evaluate the utility of PET imaging for tumor hypoxia as a predictive factor.
- To guide future therapeutic strategies by understanding patient response variability.
Main Methods:
- Assessed plasma immune biomarkers, immune cell function, and peripheral blood cytology.
- Evaluated tumor characteristics, including [64Cu]ATSM PET imaging for hypoxia.
- Correlated pretreatment variables with the development of an inflammatory response post-CNV-NT therapy.
Main Results:
- Dogs with an inflammatory response had higher heart rates, larger tumor volumes, and greater [64Cu]ATSM SUVmax.
- Increased constitutive leukocyte IL-10 production, enhanced NK cell-like function, and higher lymphocyte counts were observed.
- Unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume were the strongest predictors of inflammatory response.
Conclusions:
- Pretreatment unstimulated leukocyte IL-10 production is a key predictor of inflammatory response to CNV-NT.
- Heart rate and gross tumor volume also significantly predict the development of inflammation.
- These factors can help anticipate patient response to CNV-NT therapy.
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