Small cell lung cancer-associated tumor antigens (SCLC-TAs) (SCLC-TAs)

Small cell lung cancer (SCLC)-associated tumor antigens are a heterogeneous group of molecules, including proteins like Delta-like ligand 3 (DLL3), B7-H3 (CD276), and CD56 (NCAM1), that are preferentially expressed on the surface of SCLC cells (Gazdar et al., 2017, Nature Reviews Cancer). These antigens are often associated with the neuroendocrine origin of the disease and contribute to tumor growth, survival, and immune system evasion (Oser et al., 2015, JCO). Due to the aggressive nature of SCLC and its poor prognosis with conventional therapies, these antigens are being extensively utilized as targets for next-generation therapeutics. Current drug development strategies include bispecific T-cell engagers (BiTEs) like tarlatamab, which targets DLL3, and antibody-drug conjugates (ADCs) like ifinatamab deruxtecan, which targets B7-H3 (Paz-Ares et al., 2023, NEJM; Johnson et al., 2023, JCO). While these targets offer a path toward precision medicine in SCLC, therapeutic success is often limited by intratumoral heterogeneity and the potential for "on-target, off-tumor" toxicities in healthy tissues that express low levels of the antigens (Saunders et al., 2015, Sci Transl Med). Furthermore, the dynamic nature of antigen expression can lead to resistance through antigen loss or downregulation during treatment. Despite these challenges, the identification of these antigens has revolutionized the SCLC treatment landscape, moving beyond non-specific cytotoxic chemotherapy.

Other names

SCLC antigensSmall cell lung cancer antigensSCLC surface markersSCLC-associated antigens

These antigens serve as specific binding sites for immunotherapies, including bispecific T-cell engagers (BiTEs) and antibody-drug conjugates (ADCs), which facilitate targeted tumor cell lysis or delivery of cytotoxic payloads (Paz-Ares et al., 2023, NEJM; Johnson et al., 2023, JCO).