Abstract 2861: Targeting cancer with antibody-drug conjugates: Promises and challenges

Abstract

Abstract Chemotherapy is inherently associated with side effects due to its poor selectivity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology promises to overcome barriers of classical chemotherapy by utilizing monoclonal antibodies to deliver potent payloads to selected target cancer cells. The antibody and cytotoxic payload are joined by a chemical linker resulting in an agent with the prospect of increased selectivity, anti-cancer activity, and improved systemic circulation. As of 2019, the US Food and Drug Administration (FDA) has approved five ADCs with cancer indications, including brentuximab vedotin for treatment of CD30-expressing lymphomas, trastuzumab emtansine for Her2-positive breast cancer, inotuzumab ozogamicin for CD22-positive acute lymphoblastic leukemia (ALL), gemtuzumab ozogamicin for CD33-positive acute myeloid leukemia (AML), and polatuzumab vedotin for diffuse large B-cell lymphoma (DLBCL). Currently, there are about 80 ADCs under clinical development in nearly 130 clinical trials. Despite initial success, there are still many challenges in the development of ADCs with respect to their safety and efficacy profiles. In this study, we aim to survey the recent efforts in the design and development of ADCs. We have focused on site-specific conjugation methods for producing homogenous ADCs with consistent drug-antibody ratio (DAR) - a challenge often observed in conventional conjugation methods. This information is further discussed with respect to the ADC interaction with target cells to elicit cytotoxicity. The survey results will be presented, giving perspective on technical considerations for ADC design towards better correlation between preclinical and clinical results and overall safer and more efficacious products. Citation Format: Alexis Dean, Julianne Twomey, Baolin Zhang. Targeting cancer with antibody-drug conjugates: Promises and challenges [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2861.