Journal: Pharmaceutics

Article Title: CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models

doi: 10.3390/pharmaceutics17081049

Figure Lengend Snippet: Structure, property and selectivity of CUSP06. ( A ) Schematic structure of CUSP06. ( B ) Size exclusion chromatogram of CUSP06 indicates CUSP06 is homogenous in solution. ( C ) In vitro plasma stability of CUSP06 in buffer (PBST + 1% BSA), human, rat and monkey plasma. ( D ) Binding affinity of CUSP06 to human, monkey, rat and mouse CDH6. ( E ) Binding selectivity of CUSP06 for human CDH6, CDH9 and CDH10 by ELISA.

Article Snippet: The human, monkey, rat and mouse CDH6 recombinant proteins were purchased from Sino Biological and ACRO Biosystems.

Techniques: In Vitro, Clinical Proteomics, Binding Assay, Enzyme-linked Immunosorbent Assay

Journal: Pharmaceutics

Article Title: CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models

doi: 10.3390/pharmaceutics17081049

Figure Lengend Snippet: In vitro Characterization of CUSP06. ( A ) Internalization of CUSP06 in two ovarian cancer cell lines, OVCAR3 and PA-1. ( B ) Determination of DNA damage and apoptosis caused by CUSP06 in OVCAR3 cells. After OVCAR-3 cells were treated with CUSP06, CUSP06 mAb, IgG-ADC control or exatecan for 72 h, pChk1, total Chk1, p-H2AX, cleaved PARP, and β-actin level were detected by Western Blot. ( C ) Characterization of the antiproliferative activities of CUSP06 in CDH6-positive (OVCAR3 and PA-1) and CDH6-null ES2 cells by CCK8 assay. ( D ) Characterization of in vitro bystander effect of CUSP06. A mixture of OVCAR3 cells and ES-2-GFP cells were treated with 1.25 nM IgG-ADC, CUSP06, or R-DXd for 5 days. The viable cell numbers were determined by FACS analysis.

Article Snippet: The human, monkey, rat and mouse CDH6 recombinant proteins were purchased from Sino Biological and ACRO Biosystems.

Techniques: In Vitro, Control, Western Blot, CCK-8 Assay

Journal: Pharmaceutics

Article Title: CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models

doi: 10.3390/pharmaceutics17081049

Figure Lengend Snippet: In vivo antitumor activity of CUSP06 in PDX models. ( A ) Antitumor activity of CUSP06 in a CDH6-high Ovarian PDX model (LD-1588). A single dose of 10 mg/mg CUSP06 or IgG-ADC control was administered intravenously to the tumor-bearing mice at Day 0. Each data represents mean and SEM of tumor volume or relative body weight changes. Each group contained five mice. ( B ) Antitumor activity of CUSP06 in a CDH6-low Ovarian PDX model (LD-2851). A single dose of 3 mg/mg CUSP06 or IgG-ADC control was administered intravenously to the tumor-bearing mice at Day 0. Each data represents mean and SEM of tumor volume or relative body weight changes. Each group contained five mice. ( C ) Antitumor activity of CUSP06 in a CDH6-low kidney nephroblastoma PDX model (LD-2511). A single dose of 10 mg/mg CUSP06, R-DXd, R-T1000-e, or IgG-ADC control was administered intravenously to the tumor-bearing mice at Day 0. Each data represents mean and SEM of tumor volume or relative body weight changes. Each group contained five mice. ( D ) Antitumor activity of CUSP06 in a CDH6-low cholangiocarcinoma PDX model (LD-2214). A single dose of 10 mg/mg CUSP06, or IgG-ADC control was administered intravenously to the tumor-bearing mice at Day 0. Each data represents mean and SEM of tumor volume or relative body weight changes. Each group contained five mice. ( E ) Antitumor activity of CUSP06 in a CDH6-medium uterine cancer PDX model (UT3705). A single dose of 3 or 10 mg/mg CUSP06, or IgG-ADC control was administered intravenously to the tumor-bearing mice on Day 0. Each data represents mean and SEM of tumor volume or relative body weight changes. Each group contained five mice.

Article Snippet: The human, monkey, rat and mouse CDH6 recombinant proteins were purchased from Sino Biological and ACRO Biosystems.

Techniques: In Vivo, Activity Assay, Control