Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma

• Main Authors: Puey-Ling Chia, Sagun Parakh, Ming-Sound Tsao, Nhu-An Pham, Hui K. Gan, Diana Cao, Ingrid J. G. Burvenich, Angela Rigopoulos, Edward B. Reilly, Thomas John, Andrew M. Scott
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Pharmaceuticals
• Subjects: EGFR; malignant mesothelioma; 806-ADC; ⁸⁹Zr-ch806
• Online Access: https://www.mdpi.com/1424-8247/13/10/289

Epidermal growth factor receptor (EGFR) is highly overexpressed in malignant mesothelioma (MM). MAb806 is a novel anti-EGFR antibody that selectively targets a tumor-selective epitope. MAb806-derived antibody drug conjugates (ADCs), ABT-414, ABBV-221 and ABBV-322, may represent a novel therapeutic strategy in MM. EGFR and mAb806 epitope expressions in mesothelioma cell lines were evaluated using an array of binding assays, and the in vitro cell effects of ABT-414 and ABBV-322 were determined. In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor models. We also performed biodistribution and imaging studies to allow the quantitative targeting of MM by mAb806 using a ⁸⁹Zr-labeled immunoconjugate—ch806. A high EGFR expression was present in all mesothelioma cell lines evaluated and mAb806 binding present in all cell lines, except NCIH-2452. ABT-414 and ABBV-322 resulted in significant tumor growth inhibition in MM models with high EGFR and mAb806 epitope expressions. In contrast, in an EGFR-expressing PDX model that was negative for the mAb806 epitope, no growth inhibition was observed. We demonstrated the specific targeting of the mAb806 epitope expressing MM tumors using ⁸⁹Zr-based PET imaging. Our data suggest that targeting EGFR in MM using specific ADCs is a valid therapeutic strategy and supports further investigation of the mAb806 epitope expression as a predictive biomarker.