bioRxiv2024
In a nonclinical in vivo efficacy test for anticancer drugs, immunodeficient mice subcutaneously transplanted with human cancer cells were quantified and evaluated with regard to the manner in which the skin bulges where locally proliferated cancer cells regress after drug administration. A caliper is conventionally used to measure the tumor bulge. However, its volume is an estimated value and results in high variability. Alternatively, cancer cell lines that express genetically encoded marker genes have been used in recent years for optical and nondestructive measurements. However, estimations using calipers exhibit large errors, and biological tissues have low light transparency. This hinders quantitative optical measurements. In addition, variations in measurements owing to subjective and human operations are likely. From the chemistry, manufacturing, and control (CMC) perspective, precise measurement is required to evaluate drug efficacy and quality. Therefore, we aimed to eliminate errors caused by the use of estimated values, subjectivity, and human manipulation by precisely quantifying the volume of the tumor bulge using a 3D scanner. This study demonstrated that optical 3D scanner measurements were accurate, had low variability, and was highly correlated with tumor weight. The tumor bulge was observed to vary to a flattened oval dome shape rather than a semicircle. This caused high variability in measurements of tumor volume. However, the proposed 3D scanner was more sensitive to volumetric regression than the caliper. Additionally, it exhibited drug efficacies with higher resolution than the caliper. Furthermore, the high linearity of the scanner provided more accurate measurements over a wider range of tumor sizes than luminescence imaging. The accurate and sensitive properties of such 3D scanners are also likely to make these exceptionally effective analytical tools for ensuring product equivalency when modifying raw materials or manufacturing processes in the development of cell therapy products. As described above, robust and accurate drug efficacy measurements using nondestructive and noninvasive 3D scanners that require no training and are convenient to operate provide many analytical improvements and advantages. This is likely to play an important role in 1) the efficacy evaluation of cell therapy products that have large variations originating from the raw materials and large differences between manufacturing lots and 2) the quality evaluation, property analysis of the characteristics of variations in the shape of tumor bulges over time, and comparability testing of the products in the CMC section of pharmaceutical companies.