Delta-like ligand 3 (DLL3)-based enrichment enables sensitive and specific detection of circulating tumor cells during immunotherapy in small-cell lung cancer
Presenter: Hyung-Joo Oh, MD Session: Circulating Tumor Cells, Metastasis, and Dissemination Biology 1 Time: 4/19/2026 2:00:00 PM → 4/19/2026 5:00:00 PM
Authors
Hyung-Joo Oh 1 , Hyun-Ju Cho 1 , Seung-Hee Song 1 , Yoo-Duk Choi 2 , Woo-Jae Son 3 , Jin-Han Bae 3 , In-Jae Oh 1 , Young-Chul Kim 1 , Hae Ung Lee 3 , Cheol-Kyu Park 1 1 Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeollanam-do, Korea, Republic of, 2 Pathology, Chonnam National University Medical School, Gwangju, Korea, Republic of, 3 CTCELLS, Inc., Seoul, Korea, Republic of
Abstract
Background: Delta-like Ligand 3 (DLL3), a Notch receptor ligand, is highly expressed in small cell lung cancer (SCLC) and has emerged as a promising therapeutic target. Circulating tumor cells (CTCs), abundant in SCLC, interact with diverse immune cell populations in peripheral blood. This study investigates the potential of DLL3 as a biomarker to enhance CTC detection and monitor immunotherapy response in SCLC. Methods: We enrolled 17 patients with extensive-stage (ES) SCLC and 5 with stage IV non-small cell lung cancer (NSCLC; as controls), all scheduled for an immune checkpoint inhibitor or a bispecific T-cell engager. Whole blood (6 mL) was collected before and during treatment. CTCs were enriched using CTCeptor TM , a fully automated, negative depletion-based continuous centrifugal microfluidic system, and classified into three phenotypes: pan-cytokeratin (CK) + /DLL3 - /CD45 - , CK - /DLL3 + /CD45 - , or CK + /DLL3 + /CD45 - . Baseline tumor samples were analyzed by immunohistochemistry for SCLC molecular subtypes and DLL3. Results: DLL3 + /CD45 - CTCs were detected in all ES-SCLC patients (100%) prior to treatment with atezolizumab plus chemotherapy or tarlatamab, with a median count of 23 (range 7-121) and a median size of 9.71 μm (7.33-12.18). In contrast, no DLL3 + /CD45 - CTCs were detected in NSCLC patients, where only CK + /DLL3 - /CD45 - CTCs were observed (1-4 cells). Among ES-SCLC patients, CK - /DLL3 + /CD45 - cells were the predominant subtype (63.3%, 522/825), while CK + /DLL3 + /CD45 - CTCs accounted for 27.7% (228/825) of all detected CTCs, representing additional CTCs not captured by CK-based detection alone. ASCL1 was the most prevalent molecular subtype (12/17), with DLL3 exhibiting the highest H-score (median, 185; range, 20-300). Notably, no correlation was observed between the number or proportion of DLL3 + CTC and the DLL3 H-score ( r = -0.163, p = 0.578), while DLL3 + CTCs remained prevalent in NERUDO1 and POU2F3 subtypes. Furthermore, both total and DLL3 + CTC counts markedly decreased within 2 cycles of atezolizumab chemotherapy or 1 week after tarlatamab treatment. Conclusion: DLL3 + CTCs can be efficiently and specifically detected in ES-SCLC patients using CTCeptor TM , serving as a complementary marker to CK for CTC identification. DLL3 appears more frequently in CTCs than in tumor tissue. These findings support DLL3 as a potential biomarker for CTC-based monitoring in ES-SCLC and warrant further validation in larger cohorts, including analyses of immunologic features.
Disclosure
H. Oh, None.. H. Cho, None.. S. Song, None.. Y. Choi, None. W. Son, CTCELLS, Inc. Employment. J. Bae, CTCELLS, Inc. Employment. I. Oh, None.. Y. Kim, None. H. Lee, CTCELLS, Inc. Employment. C. Park, None.
Cited in
Control: 1921 · Presentation Id: 10252 · Meeting 21436