Abstract IA017: Transferrin receptor targeting chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins in cancer

Abstract

Abstract The membrane and extracellular proteome plays central roles in health and disease. Harnessing TfR1, a constitutive, rapidly internalizing receptor overexpressed in a broad spectrum of cancers, we developed Transferrin Receptor Targeting Chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins. In two applications, we show that TransTACs enabled the targeting of drug-resistant epidermal growth factor receptor (EGFR)-driven lung cancer and the reversible control of primary Chimeric Antigen Receptor (CAR)-T cells. TransTACs represent a promising new family of bifunctional antibodies for precise manipulation of membrane proteins and for targeted cancer therapy. Citation Format: Xin Zhou. Transferrin receptor targeting chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA017.