Supplemental Figures and Table from Preclinical Antitumor Activity of a Novel Anti–c-KIT Antibody–Drug Conjugate against Mutant and Wild-type c-KIT–Positive Solid Tumors
Year: 2023
Type: supplementary-materials
Abstract: Figure S1. RNASeq data across multiple tumor types indicate c-KIT overexpression in a subset of cancer types such as AML, melanoma, testicular germ cell cancer and lung cancer. This was obtained from the TCGA data set. Figure S2. Western blot analysis of phosphorylated c-KIT and total c-KIT protein levels. Cells were starved overnight in 0.1% serum and then left untreated or treated with 10 ng/ml of SCF +/- 5 ug/ml of ADC together for 15 minutes before preparing cell lysates for immunoblotting. Figure S3. Correlation between c-KIT expression level and sensitivity to LOP628. GIST, SCLC and AML cell lines were analyzed for surface c-KIT expression by flow cytometry and assessed for sensitivity to LOP cell proliferation assays. Sensitivity to LOP628 was enriched if the cell line expressed >20,000 surface c-KIT receptors. Figure S4. Representative images of c-KIT immunostained GIST-T1, GIST430, NCI-H1048 and NCI-H2170 tumor xenografts in SCID-beige mice Figure S5. Lack of LOP628 efficacy in the c-KIT low/negative NCI-H2170 tumor xenograft model in SCID-beige mice after a single 10 mg/kg i.v. dose. Table S1. Activity of antagonist vs non-ligand blocking c-Kit ADCs in panel of GIST, AML and SCLC cell lines. Cell line sensitivity to the S-DM1-ME payload was also evaluated. There were no significant differences in activity between the two classes of ADCs. (A) refers to antagonist or ligand-blocking Abs. Table S2. Surface c-KIT expression on human and cynomolgus monkey mast cells and bone marrow cells as quantified by IHC or flow cytometry.
Authors: Tinya Abrams, Anu Connor, Christie Fanton, Steven B. Cohen, Thomas Huber, Kathy Miller, E. Erica Hong, Xiaohong Niu, Janine Kline, Marjorie Ison-Dugenny, Sarah Harris, Dana Walker, Klaus Krauser, Francesco Galimi, Zhen Wang, Majid Ghoddusi, Keith Mansfield, Si Tuen Lee-Hoeflich, Jocelyn Holash, Nancy Pryer, William Kluwe, Seth A. Ettenberg, William R. Sellers, Emma Lees, Paul Kwon, Judith A. Abraham, Siew C. Schleyer
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362405595