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Advances in DLL3-targeted therapies for small cell lung cancer: challenges, opportunities, and future directions.
Front Oncol
December 2024
Taylor's University, Subang Jaya, Selangor, Malaysia.
Small cell lung cancer (SCLC) remains one of the most aggressive and challenging malignancies to treat, with limited therapeutic options and poor outcomes. Recent advances in understanding SCLC biology have identified Delta-like ligand 3 (DLL3) as a promising target for novel therapies. This review explores the evolving landscape of DLL3-targeted therapies in SCLC, examining their mechanistic basis, preclinical promise, and clinical development.
View Article and Find Full Text PDFDB-1314, a novel DLL3-targeting ADC with DNA topoisomerase I inhibitor, exhibits promising safety profile and therapeutic efficacy in preclinical small cell lung cancer models.
J Transl Med
August 2024
Department of Research and Development, Duality Biologics, LTD, Unite 1106 868 Yinghua Road, Unite, 1106, 201204, Shanghai, P.R. China.
Background: Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target for SCLC. However, none of the DLL3-targeting antibody-drug conjugates (ADCs) have been approved for SCLC therapy yet. We developed DB-1314, the new anti-DLL3 ADC composed of a novel humanized anti-DLL3 monoclonal antibody (DB131401) conjugated with eight molecules of P1021 (topoisomerase I inhibitor), and described its preclinical profiles.
View Article and Find Full Text PDFImaging with [Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial.
Lancet Oncol
August 2024
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA. Electronic address:
Background: Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.
View Article and Find Full Text PDFFZ-AD005, a Novel DLL3-Targeted Antibody-Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models.
Mol Cancer Ther
October 2024
Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd., Shanghai, China.
Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody-drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine.
View Article and Find Full Text PDFDLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy.
Mol Cancer
May 2024
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 494 Biomedical Research Tower, 460 W 10th Ave., Columbus, OH, 43210, USA.
Article Synopsis
- * Various therapies targeting DLL3 include antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapies, with tarlatamab showing promising results and currently under FDA review.
- * Ongoing clinical trials are set to assess the effectiveness of DLL3-targeted therapies, including novel T-cell engagers and radiotherapy, emphasizing the need for further research to improve treatment outcomes for SCLC patients.
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