T-cell engagers in small cell lung cancer.

Abstract

The management of small cell lung cancer (SCLC) has been transformed by the advent of effective T-cell engagers (TCEs), which circumvent the traditionally immunosuppressive tumor microenvironment by directly facilitating T-cell-mediated cell lysis. Delta-like ligand 3 (DLL3) has emerged as the predominant target for TCE development in SCLC given its high expression on tumor cells and relatively spared expression on normal tissues. Tarlatamab, a DLL3xCD3 TCE that is now an approved agent for SCLC, has revolutionized outcomes for patients with SCLC, but raises challenges in terms of toxicity management and real-world implementation. In this review, we discuss the current landscape and future directions of DLL3-targeting TCE in SCLC, including accumulating real-world clinical experience, nascent investigation into patient selection and modifiers of response and resistance, and anticipated paradigm shifts as a result of ongoing clinical trials.