Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer

Surface protein targeting therapies, such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BiTEs) and chimeric antigen receptor (CAR) T cells are an exciting emerging class of cancer therapies. In this talk, we will discuss how to harness these surface proteins to build effective therapeutic and imaging agents, and how to modulate their expression in cancer cells to improve targeting efficacy. Using DLL3 as an example target in small-cell/neuroendocrine prostate cancer (SCNC), we will demonstrate how AMG 757 (tarlatamab), a half-life extended BiTE immunotherapy, redirects CD3-positive T cells to kill DLL3-expressing patient-derived xenografts (PDX) models of SCNC and provide long-term, durable tumor control in mouse models. We will explore how heterogeneity of DLL3 expression impacts response to AMG 757 and provide data on how PET imaging agents may help us with patient selection, as these therapies enter into clinical trials. Finally, we will explore methods to prime tumors and enhance surface protein target expression, which can lead to improved tumor control.