ArticleProceedings of the National Academy of Sciences of the United States of America2022
Combination of tucatinib and neural stem cells secreting anti-HER2 antibody prolongs survival of mice with metastatic brain cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Cancer stem cells synthesize proline to attenuate oxidative stress.The Journal of clinical investigation · 2026Article
- Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular imaging of tucatinib-induced cellular and TME changes in preclinical models of HER2 + breast cancer.Breast cancer research and treatment · 2026Article
- Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis.Frontiers in pharmacology · 2026Article
- Targeting Ischemic Stroke with Neural Stem Cells: Insights into Endogenous Repair Mechanisms, Biomaterial-Based Delivery, and Exosome Therapies.Molecular neurobiology · 2025Review
- Reelin-LRP8 signaling mediates brain dissemination of breast cancer cells via abluminal migration.EMBO molecular medicine · 2025Article
- Anti-HER2-targeted therapies: effects on humanFrontiers in drug delivery · 2025Article
- Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies.Frontiers in immunology · 2024Review
- Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases.Nature cancer · 2023Article
- Breast cancer brain metastasis: Current evidence and future directions.Cancer medicine · 2023Review
- Microenvironment and the progress of immunotherapy in clinical practice of NSCLC brain metastasis.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Brain metastases are a leading cause of death in patients with breast cancer. The lack of clinical trials and the presence of the blood-brain barrier limit therapeutic options. Furthermore, overexpression of the human epidermal growth factor receptor 2 (HER2) increases the incidence of breast cancer brain metastases (BCBM). HER2-targeting agents, such as the monoclonal antibodies trastuzumab and pertuzumab, improved outcomes in patients with breast cancer and extracranial metastases. However, continued BCBM progression in breast cancer patients highlighted the need for novel and effective targeted therapies against intracranial metastases. In this study, we engineered the highly migratory and brain tumor tropic human neural stem cells (NSCs) LM008 to continuously secrete high amounts of functional, stable, full-length antibodies against HER2 (anti-HER2Ab) without compromising the stemness of LM008 cells. The secreted anti-HER2Ab impaired tumor cell proliferation in vitro in HER2+ BCBM cells by inhibiting the PI3K-Akt signaling pathway and resulted in a significant benefit when injected in intracranial xenograft models. In addition, dual HER2 blockade using anti-HER2Ab LM008 NSCs and the tyrosine kinase inhibitor tucatinib significantly improved the survival of mice in a clinically relevant model of multiple HER2+ BCBM. These findings provide compelling evidence for the use of HER2Ab-secreting LM008 NSCs in combination with tucatinib as a promising therapeutic regimen for patients with HER2+ BCBM.
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