ArticleTranslational oncology2021
Rova-T enhances the anti-tumor activity of anti-PD1 in a murine model of small cell lung cancer with endogenous Dll3 expression.
Article in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Pan-cancer analysis of Notch pathway-linked gene expression identifies tumour-specific and sex-stratified prognostic associations.Clinical and translational radiation oncology · 2026Article
- The current and emerging immunotherapy paradigm in small-cell lung cancer.Nature cancer · 2025Review
- Targeting DLL3: Innovative Strategies for Tumor Treatment.Pharmaceutics · 2025Review
- The Potential of Single-Transcription Factor Gene Expression by RT-qPCR for Subtyping Small Cell Lung Cancer.International journal of molecular sciences · 2025Article
- Heterogeneity of molecular subtyping and therapy-related marker expression in primary tumors and paired lymph node metastases of small cell lung cancer.Virchows Archiv : an international journal of pathology · 2025Article
- CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors.Cell reports. Medicine · 2024Article
- Article
- Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody-Drug Conjugates.Cancers · 2023Review
- Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.Journal of hematology & oncology · 2023Review
- Review
- Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.Frontiers in genetics · 2023Article
- Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy.Theranostics · 2023Review
- Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.International journal of molecular sciences · 2022Review
- Infiltrating T lymphocytes in the tumor microenvironment of small cell lung cancer: a state of knowledge review.Journal of cancer research and clinical oncology · 2022Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rovalpituzumab tesirine (Rova-T) offers a targeted therapy for ~85% of SCLC patients whose tumors express DLL3, but clinical dosing is limited due to off-target toxicities. We hypothesized that a sub-efficacious dose of Rova-T combined with anti-PD1, which alone shows a clinical benefit to ~15% of SCLC patients, might elicit a novel mechanism of action and extend clinical utility. Using a pre-clinical murine SCLC tumor model that expresses Dll3 and has an intact murine immune system, we found that sub-efficacious doses of Rova-T with anti-PD1 resulted in enhanced anti-tumor activity, compared to either monotherapy. Multiplex immunohistochemistry (IHC) showed CD4 and CD8 T-cells primarily in normal tissue immediately adjacent to the tumor. Combination treatment, but not anti-PD1 alone, increased Ki67+/CD8 T-cells and Granzyme B+/CD8 in tumors by flow cytometry and IHC. Antibody depletion of T-cell populations showed CD8+ T-cells are required for in vivo anti-tumor efficacy. Whole transcriptome analysis as well as flow cytometry and IHC showed that Rova-T activates dendritic cells and increases Ccl5, Il-12, and Icam more than anti-PD1 alone. Increased tumor expression of PDL1 and MHC1 following Rova-T treatment also supports combination with anti-PD1. Mice previously treated with Rova-T + anti-PD1 withstood tumor re-challenge, demonstrating sustained anti-tumor immunity. Collectively our pre-clinical data support clinical combination of sub-efficacious Rova-T with anti-PD1 to extend the benefit of immune checkpoint inhibitors to more SCLC patients.
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