Abstract 743: ABT-806-derived antibody-drug conjugates (ADCs) inhibit growth of malignant mesothelioma in vivo

Abstract

Abstract Introduction: Malignant mesothelioma (MM) is an aggressive malignancy of the pleura with limited therapeutic options, and is associated with a poor prognosis. EGFR is known to be highly over-expressed in mesothelioma with reported EGFR overexpression between 44 to 97%. We have developed an anti-EGFR antibody (ABT-806), which is tumour specific and robustly inhibits EGFR-expressing tumours. We aimed to establish the validity and feasibility of targeting tumour expressed EGFR in MM using ABT-806 novel ADCs (ABT-414 and ABBV-221). Methods: We evaluated EGFR and mAb 806 immunohistochemistry in 4 MM cell lines (MSTO-211H, NCI-H2052, NCI-H28, NCI-H2452) and performed in-vitro cell proliferation assays (CPA) to evaluate the antineoplastic potential of mAb806-related ADCs. In-vivo therapeutic studies using the biphasic mesothelioma cell line (MSTO-211H) were conducted with treatment groups involving ABT-414, ABBV-221, ADC control, cisplatin chemotherapy. We also performed quantitative biodistribution and imaging of mAb806 ADC uptake (89Zr mAb806 ADC) to allow correlation of mAb806 ADC concentration in tumours. Results: mAb806 elicited strong binding to three of four MM cell lines (MSTO-211H, NCI-H2052 and NCI-H28). CPAs also demonstrated ABT-414 and ABBV- 221 had significant cell growth inhibition demonstrated in the range between 1 to 10ug/ml for MM cell lines. In MSTO-211H xenograft model significant anti-tumour response to both ABT-414 and ABBV-221 (p<0.01), was demonstrated. High, specific targeting of 89Zr-ch806 to MM tumour in-vivo was also shown. Conclusion: ABT-806 ADCs show potent anti-tumour activity in MM model, and warrant further exploration as a potential therapy for MM. Citation Format: Puey Ling Chia, Diana Cao, Angela Rigopoulos, Hui Gan, Ed Reilly, Andrew Phillips, Thomas John, Andrew M. Scott. ABT-806-derived antibody-drug conjugates (ADCs) inhibit growth of malignant mesothelioma in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 743.