Journal: Cell Reports Medicine

Article Title: Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor

doi: 10.1016/j.xcrm.2025.102213

Figure Lengend Snippet: Identification of CDH17 as a potential therapeutic target for GI cancers (A) Schematic overview of the multi-omics strategy for identifying gastrointestinal cancer markers. Key steps included (I) selection of genes upregulated in tumors vs. normal tissues, (II) exclusion of genes highly expressed in normal organs (organ images from Figdraw), (III) removal of markers expressed on immune cells, and (IV) identification of tumor epithelium-specific genes. The top five colorectal cancer candidates and a representative simulated protein structure are shown (V). Statistical analyses were performed in R 4.2.2. (B) CDH17 expression analysis in gastrointestinal cancer tissue microarrays. H-scores and sample numbers are detailed in . Representative IHC images show variable staining intensities. Data are represented as mean ± SEM. (C) CDH17 surface expression in gastrointestinal cancer cell lines, as assessed by flow cytometry. Negative controls included primary endothelial cells and non-cancerous cell lines. Data are represented as mean ± SEM. (D and E) CDH17 mRNA (D) and protein (E) expression levels across CRC CMS1–4 subtypes using TCGA and clinical sample data, respectively. Data are presented as mean ± SEM. (F) Summary of CDH17 expression in CRC PDX models by molecular subtype. Data are represented as mean ± SEM. Statistical significance was determined by Kruskal-Wallis test in (D)–(F). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, and ∗∗∗∗p < 0.0001. See also and and .

Article Snippet: Human tumor cell lines were obtained from ATCC (via Cobioer, Nanjing, China) or DSMZ, and recombinant rhesus CDH17 cell lines from Genomeditech (Shanghai).

Techniques: Biomarker Discovery, Selection, Expressing, Staining, Flow Cytometry

Journal: Cell Reports Medicine

Article Title: Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor

doi: 10.1016/j.xcrm.2025.102213

Figure Lengend Snippet: Generation and characterization of anti-CDH17 ADC 7MW4911 (A) Structure of 7MW4911: the ADC consists of the MF-6 payload conjugated to Mab0727 via a linker system composed of IDconnect and PEG-VA, enabling efficient payload release. (B and C) Physicochemical properties of 7MW4911 were measured by HIC-HPLC (B) and SEC-HPLC (C). (D and E) Binding affinities of 7MW4911 to human (D) and cynomolgus monkey (E) CDH17 were measured by Octet RED96 system. (F) Binding of 7MW4911 to CDH17-expressing cell lines (SK-CO-1, SNU-C1, SNU-16) was assessed by flow cytometry. (G) CDH17-mediated internalization of 7MW4911 was evaluated in CDH17-positive cell lines. (H) Cytotoxicity of 7MW4911 was measured in cell lines with varying CDH17 expression using CellTiter-Glo assays. (I–L) Stability of 7MW4911 in cynomolgus monkey plasma. Binding activity (I and J) and concentrations (K and L) of total antibody (TAB) and intact ADC were evaluated over time, as described in the . Data in (K) and (L) are normalized to baseline values. (M) Pharmacokinetics of 7MW4911 in BALB/c mice following a single intravenous dose on day 0. Serum levels of TAB and intact ADC were quantified over time. Data are represented as mean ± SEM ( n = 4). (N) Bystander killing effect of 7MW4911 evaluated using a co-culture model. See also and .

Article Snippet: Human tumor cell lines were obtained from ATCC (via Cobioer, Nanjing, China) or DSMZ, and recombinant rhesus CDH17 cell lines from Genomeditech (Shanghai).

Techniques: Binding Assay, Expressing, Flow Cytometry, Clinical Proteomics, Activity Assay, Drug discovery, Co-Culture Assay