Activity in Group-Housed Home Cages of Mice as a Novel Preclinical Biomarker in Oncology Studies

SIMPLE SUMMARY: Improving experimental conditions in preclinical animal studies is essential. Automated digital ventilated cages offer the advantage of continuous monitoring of animal locomotor activity in their home cage over a long period, improving animal welfare through the reduction in animal handling. The potential utility of this technology remains understudied and deserves investigation in the field of oncology. Here, we determined the utility of continuous assessment of locomotor activity using the DVC(®) technology on the SCID (severe combined immunodeficiency) mouse model treated with reference oncology compounds. Our results showed that the use of the DVC(®) locomotion index is able to identify significant deleterious effects on animal activity, while suggesting perturbations of animal behaviors that would not have been detected by staff clinical assessment over a limited daytime observation. The use of this technology also helped to detect the anticipated effects of the drugs tested, highlighting the potential of this digital biomarker to differentiate treatment adverse effects in preclinical oncology studies. ABSTRACT: Background: Improving experimental conditions in preclinical animal research is a major challenge, both scientifically and ethically. Automated digital ventilated cages (DVC(®)) offer the advantage of continuous monitoring of animal activity in their home-cage. The potential utility of this technology remains understudied and deserves investigation in the field of oncology. Methods: Using the DVC(®) platform, we sought to determine if the continuous assessment of locomotor activity of mice in their home cages can serve as useful digital readout in the monitoring of animals treated with the reference oncology compounds cisplatin and cyclophosphamide. SCID mice of 14 weeks of age were housed in DVC(®) cages in groups of four and followed with standard and digital examination before and after treatment over a 17-day total period. Results: DVC(®) detected statistically significant effects of cisplatin on the activity of mice in the short and long term, as well as trends for cyclophosphamide. The activity differences between the vehicle- and chemotherapy-treated groups were especially marked during the nighttime, a period when animals are most active and staff are generally not available for regular checks. Standard clinical parameters, such as body weight change and clinical assessment during the day, provided additional and complementary information. Conclusion: The DVC(®) technology enabled the home cage monitoring of mice and non-invasive detection of animal activity disturbances. It can easily be integrated into a multimodal monitoring approach to better capture the different effects of oncology drugs on anti-tumor efficacy, toxicity, and safety and improve translation to clinical studies.