American Association for Cancer Research
Browse
10780432ccr151542-sup-151905_2_table_3184546_nw7vs7.docx (17.69 kB)

Supplemental Table 2 from AGS16F Is a Novel Antibody Drug Conjugate Directed against ENPP3 for the Treatment of Renal Cell Carcinoma

Download (17.69 kB)
journal contribution
posted on 2023-03-31, 19:03 authored by Fernando Doñate, Arthur Raitano, Kendall Morrison, Zili An, Linnette Capo, Hector Aviña, Sher Karki, Karen Morrison, Peng Yang, Jimmy Ou, Ryuichi Moriya, Yuriy Shostak, Faisal Malik, Rossana Nadell, Wendy Liu, Daulet Satpayev, John Atkinson, Ingrid B.J. Joseph, Daniel S. Pereira, Pia M. Challita-Eid, David R. Stover

Supplemental Table 2. Comparability of Anti-ENPP3 ADC Produced in Hybridoma or CHO Cells

History

ARTICLE ABSTRACT

Purpose: New cancer-specific antigens are required for the design of novel antibody–drug conjugates (ADC) that deliver tumor-specific and highly potent cytotoxic therapy.Experimental Design: Suppression subtractive hybridization identified ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3 or CD203c) as a potential human cancer-specific antigen. Antibodies targeting the extracellular domain of human ENPP3 were produced and selected for specific binding to ENPP3. Expression of ENPP3 in normal and cancer tissue specimens was evaluated by immunohistochemistry (IHC). ADCs comprising anti-ENPP3 Ab conjugated with maleimidocaproyl monomethyl auristatin F via a noncleavable linker (mcMMAF) were selected for therapeutic potential using binding and internalization assays, cytotoxicity assays, and tumor growth inhibition in mouse xenograft models. Pharmacodynamic markers were evaluated by IHC in tissues and ELISA in blood.Results: ENPP3 was highly expressed in clear cell renal cell carcinoma: 92.3% of samples were positive and 83.9% showed high expression. By contrast, expression was negligible in normal tissues examined, with the exception of the kidney. High expression was less frequent in papillary renal cell carcinoma and hepatocellular carcinoma samples. AGS16F, an anti-ENPP3 antibody–mcMMAF conjugate, inhibited tumor growth in three different renal cell carcinoma (RCC) xenograft models. AGS16F localized to tumors, formed the active metabolite Cys-mcMMAF, induced cell-cycle arrest and apoptosis, and increased blood levels of caspase-cleaved cytokeratin-18, a marker of epithelial cell death.Conclusions: AGS16F is a promising new therapeutic option for patients with RCC and is currently being evaluated in a phase I clinical trial. Clin Cancer Res; 22(8); 1989–99. ©2015 AACR.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC