Abstract 6841: Improved Ba/F3 kinase engineered cell lines: an innovative in vivo screening platform

Abstract Background: Ba/F3 engineered cells commonly cause tumor metastasis when implanted into immune-deficient mice, resulting in reduced survival time and narrower dosing windows. To overcome this limitation, we have developed a novel approach that modifies these cells without compromising target pathway activation while significantly reducing their metastatic potential. This modification extends both the survival duration and the therapeutic window available for treatment interventions. Methods: We utilized two distinct cell lines, KC-2400 Ba/F3-TPR-Met-D1228A and KC-4183-Ba/F3-plus-TPR-MET-D1228A respectively. Both cell types were implanted subcutaneously (SC) into NOD SCID female mice. Key parameters such as time to staging at 100 mm^3, time to reach 1000 mm^3, time to first death, dosing window duration, and average tumor volume (ATV) at the point of first death were meticulously recorded and compared between the two groups. Results: The modified cell line demonstrated a slower progression rate, taking 28 days to reach 1000 mm^3 compared to 18 days for the unmodified group. Survival time increased by 11 days, from 24 days to 35 days, while the therapeutic dosing window expanded from 14 days to 25 days. Futhermore, the ATV at the time of first death was reduced from approximately 1700 mm^3 to around 1300 mm^3, reflecting better tumor growth control. Conclusion: Engineering Ba/F3 cells to diminish their metastatic capability effectively prolongs survival and broadens the therapeutic window in immune-deficient mouse models. This strategy offers a promising enhancement for preclinical research and holds potential for improving therapeutic outcomes in related clinical applications. Citation Format: Hao Huang, Yunpeng Zhai, Xuyang Duan, Na Li, Siyu Li, Guoqian Wang, Jinying Ning, Feng Hao. Improved Ba/F3 kinase engineered cell lines: an innovative in vivo screening platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6841.