Abstract 6960: Specific BaF3 tumor platform for c-KIT and KRAS mutations

Abstract BaF3 cell line from mouse pro-B cell is rely on interleukin-3 (IL-3) for survival and widely used to evaluate the efficacy of kinase oncogenes, downstream signaling, and the blocking ability of small molecule kinase inhibitors by site specific mutation of target genes such as KRAS, EGFR, AKT, c-KIT, etc. However, few was known about the in vivo efficacy of BaF3 tumor models and the differences of efficacy from spontaneous mutation human cell lines. ICE bioscience constructed over 300 BaF3 point mutation stable cell lines as a good platform for high throughput screening in vitro. In this study, two specific BaF3 c-kit mutation tumor models (BaF3 c-KIT-V559-V560 del, BaF3 c-KIT-W557-K558 del-T670I) and BaF3 KRAS-G12C tumor models were established for efficacy evaluation of Imatinib, Sunitinib, and Sotorasib. The results showed that Imatinib 100 mpk inhibited BaF3 c-KIT-V559-V560 del tumor growth (TGI=111.10%, T/C=2.68%) and Sunitinib 40 mpk inhibited BaF3 c-KIT-W557-K558 del-T670I tumor growth (TGI=106.13%, T/C=2.03%), respectively. The efficacy of Sotorasib-30 mpk to Ba/F3 KRAS G12C tumor is significant and reached 89.37% TGI and 26.71% T/C. Although ASP3082 is a KRAS G12D inhibitor, the efficacy of ASP3082-3 mpk to KRAS-G12D GP2d CDX model is not relevant, only 37.29% TGI and 73.25% T/C values were found in this study. Western blotting showed that the BaF3 mutation tumor models are suitable for the drug discovery of specific point mutation anti-cancer drugs. Citation Format: Ziwei Li, Hating Dai, Tianyu Pang, Jiali Liu, Wenbo Du, Wen-Jen Yu. Specific BaF3 tumor platform for c-KIT and KRAS mutations [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 6960.