scholarly journals Human Neural Stem Cells Can Target and Deliver Therapeutic Genes to Breast Cancer Brain Metastases

2009 ◽  
Vol 17 (3) ◽  
pp. 570-575 ◽  
Author(s):  
Kyeung Min Joo ◽  
In H Park ◽  
Ji Y Shin ◽  
Juyoun Jin ◽  
Bong Gu Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells ◽  
Breast Cancer Brain Metastases ◽  
Therapeutic Genes

scholarly journals Combination of tucatinib and neural stem cells secreting anti-HER2 antibody prolongs survival of mice with metastatic brain cancer

2021 ◽  
Vol 119 (1) ◽  
pp. e2112491119
Author(s):  
Alex Cordero ◽  
Matthew D. Ramsey ◽  
Deepak Kanojia ◽  
Jawad Fares ◽  
Edgar Petrosyan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Human Neural Stem Cells ◽  
Breast Cancer Brain Metastases

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.

scholarly journals Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases

Stem Cells ◽  
2015 ◽  
Vol 33 (10) ◽  
pp. 2985-2994 ◽  
Author(s):  
Deepak Kanojia ◽  
Irina V. Balyasnikova ◽  
Ramin A. Morshed ◽  
Richard T. Frank ◽  
Dou Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Preclinical Model ◽  
Breast Cancer Brain Metastases

scholarly journals SCIDOT-22. INTRACEREBROVENTRICULAR DELIVERY OF TUMOR-HOMING CYTOTOXIC HUMAN INDUCED NEURAL STEM CELLS FOR TREATMENT OF BRAIN METASTASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi276-vi276
Author(s):  
Wulin Jiang ◽  
Alison Mercer-Smith ◽  
Juli Bago ◽  
Simon Khagi ◽  
Carey Anders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Tumor Homing ◽  
Migration Assays ◽  
Induced Neural Stem Cells ◽  
First Time ◽  
The Brain

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) and breast cancer are the most common cancers that metastasize to the brain. New therapies are needed to target and eradicate metastases. We have developed genetically-engineered induced neural stem cells (hiNSCs) derived from human fibroblasts that selectively home to tumors and release the cytotoxic protein TRAIL. Building on these results, we explored the efficacy of hiNSC therapy delivered via intracerebroventricular (ICV) injections for the treatment of metastatic foci in the brain for the first time. METHODS We performed in vitro efficacy and migration assays in conjunction with in vivo studies to determine the migration, persistence, and efficacy of therapeutic hiNSCs against H460 NSCLC and triple-negative breast cancer MB231-Br tumors in the brain. Following the establishment of tumors in the brains of nude mice, hiNSCs were injected directly into the tumor or the ventricle contralateral to the tumor. The migration and persistence of hiNSCs were investigated by following the bioluminescence of the hiNSCs. The therapeutic efficacy of the hiNSCs was determined by following the bioluminescence of the tumor. RESULTS/ CONCLUSION Co-culture results demonstrated that hiNSC therapy reduced the viability of H460 and MB231-Br up to 75% and 99.8% respectively compared to non-treated controls. In vitro migration assays showed significant directional migration toward both lung and breast cancer cells within 4 days. ICV-administered hiNSC serial imaging shows that cells persisted for >1 week in the brain. Fluorescent analysis of tissue sections showed that hiNSCs co-localized with lateral and contralateral tumors within 7 days. Using H460 and MB231-Br models, kinetic tracking of intracranial tumor volumes showed intratumoral or ICV-injected therapeutic hiNSCs suppressed the growth rate of brain tumors by 31-fold and 3-fold, respectively. This work demonstrates for the first time that we can effectively deliver personalized cytotoxic tumor-homing cells through the ventricles to target brain metastases.

Antithyroid cancer effects of human neural stem cells expressing therapeutic genes on anaplastic thyroid cancer cells

2019 ◽  
Vol 121 (2) ◽  
pp. 1586-1598
Author(s):  
Hye‐Ji Shin ◽  
Kyung‐A. Hwang ◽  
Ryeo‐Eun Go ◽  
Seung U. Kim ◽  
Kyung‐Chul Choi
Keyword(s):  
Stem Cells ◽  
Thyroid Cancer ◽  
Neural Stem Cells ◽  
Cancer Cells ◽  
Anaplastic Thyroid Cancer ◽  
Human Neural Stem Cells ◽  
Thyroid Cancer Cells ◽  
Therapeutic Genes

Genetically engineered human neural stem cells with rabbit carboxyl esterase can target brain metastasis from breast cancer

2011 ◽  
Vol 311 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Ho Jun Seol ◽  
Juyoun Jin ◽  
Dong-Ho Seong ◽  
Kyeung Min Joo ◽  
Wonyoung Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastasis ◽  
Neural Stem Cells ◽  
Genetically Engineered ◽  
Human Neural Stem Cells ◽  
Carboxyl Esterase

scholarly journals BMET-40NANO PLATFORM FOR DYNAMIC IN VIVO TRACKING OF NEURAL STEM CELLS TO BRAIN METASTASES OF BREAST CANCER

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v53.5-v54
Author(s):  
Dou Yu ◽  
Shih-Hsun Cheng ◽  
Hsiu-Ming Tsai ◽  
Deepak Kanojia ◽  
Lara Leoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells

scholarly journals mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1043 ◽  
Author(s):  
Phil Jun Kang ◽  
Daryeon Son ◽  
Tae Hee Ko ◽  
Wonjun Hong ◽  
Wonjin Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Urine ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Patient Specific ◽  
Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

scholarly journals BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

2021 ◽  
Vol 22 (8) ◽  
pp. 3913
Author(s):  
Satoshi Nakata ◽  
Ming Yuan ◽  
Jeffrey A. Rubens ◽  
Ulf D. Kahlert ◽  
Jarek Maciaczyk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Tandem Duplication ◽  
Target Genes ◽  
Cellular Growth ◽  
Central Nervous System Tumor ◽  
Internal Tandem Duplication ◽  
Invasion And Migration ◽  
Human Neural Stem Cells ◽  
And Migration

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.

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