Abstract 7503: Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice
Authors: Pak Sehyung , Pak Hajin , Yoo Hee Jin , Min Sra , Kim Hui Ji , Lee JaeYoon , Song Min-Ji , Choi Jaesung , Jeong Aejin , Kim Hanbyeol , Kim Jung Won , Lee Hai-Chon 
Published: March 2024

Circulating tumor cells (CTCs) possess the potential to serve as innovative markers in clinical trials, contributing to the understanding of cancer metastasis mechanisms, diagnosis, prognosis, the development of personalized treatment strategies, and enabling the monitoring of treatment efficacy. NSG mice, which are a strain of immunodeficient mice frequently utilized as a non-clinical model for cancer research, exhibit diminished levels of natural killer (NK) cells and abnormal monocytes in their bloodstream. In a previous study, a positive correlation was observed between the duration of injection and the levels of white blood cells (WBC) in mice that were injected with various cancer cell lines derived from humans. To evaluate the correlation among the primary tumor and circulating tumor cells (CTCs), as well as the impact on immune cells, we assessed changes in immune cell composition, primary tumor size, and enumeration of CTCs in xenografted mice over a period of time. This investigation was carried out using CytoGen's Smart Biopsy™ systems. The results, which were obtained using equipment including CytoGen's Smart Biopsy™ Systems, showed that the distribution of white blood cell (WBC) components exhibited variations based on age, primary tumor burden, and circulating tumor cell (CTC) count following injection. A notable association was observed between the augmentation of immune cells and the quantity of circulating tumor cells (CTCs) present in the bloodstream. Therefore, alterations in immune cells may potentially impact the potential to affect the ability to influence the efficacy of cancer immunotherapy, metabolic therapy, and anti-metastatic therapy. When conducting non-clinical investigations with the objective of developing cancer treatment protocols, it is crucial to meticulously select humanized or immunodeficient mice that are appropriate for the study. Therefore, it is advisable to perform regular monitoring of murine blood samples in order to observe any variations in the counts of circulating tumor cells (CTCs), while considering a standardized blood volume per individual. In the immunodeficient mouse model, the existence of circulating tumor cells (CTCs) results in an increase in the quantity of cells present in the bloodstream. The observed rise in circulating tumor cells (CTCs) is found to be concurrent with the progression and development of the primary tumor. The consideration of this aspect is of utmost importance in the formulation of non-clinical studies aimed at the development of cancer treatment protocols.

Citation Format: Sehyung Pak, Hajin Pak, Hee Jin Yoo, Sra Min, Hui Ji Kim, JaeYoon Lee, Min-Ji Song, Jaesung Choi, Aejin Jeong, Hanbyeol Kim, Jung Won Kim, Hai-Chon Lee. Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7503.