Selective delivery of a therapeutic gene for treatment of head and neck squamous cell carcinoma using human neural stem cells

Seong Keun Kwon, Seung U. Kim, Jae-Jun Song, Chang Gun Cho, Seok Won Park

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives. Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods. To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results. In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion. Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

Original languageEnglish
Pages (from-to)176-183
Number of pages8
JournalClinical and Experimental Otorhinolaryngology
Volume6
Issue number3
DOIs
Publication statusPublished - 2013 Sep 1
Externally publishedYes

Fingerprint

Neural Stem Cells
Flucytosine
Genes
Cytosine Deaminase
Therapeutics
Nude Mice
Fluorouracil
Cell Line
Injections
Tropism
Carcinoma, squamous cell of head and neck
Prodrugs
Enzymes
Tumor Burden
Brain Neoplasms
Intravenous Injections
Antineoplastic Agents
Suicide
Neoplasms
Transplantation

Keywords

  • Cytosine deaminase
  • Head and neck neoplasms
  • Molecular targeted therapy
  • Neural stem cells
  • Tropism

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Selective delivery of a therapeutic gene for treatment of head and neck squamous cell carcinoma using human neural stem cells. / Kwon, Seong Keun; Kim, Seung U.; Song, Jae-Jun; Cho, Chang Gun; Park, Seok Won.

In: Clinical and Experimental Otorhinolaryngology, Vol. 6, No. 3, 01.09.2013, p. 176-183.

Research output: Contribution to journalArticle

@article{f13f24f431de4c4a8f110a6f55b7331c,
title = "Selective delivery of a therapeutic gene for treatment of head and neck squamous cell carcinoma using human neural stem cells",
abstract = "Objectives. Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods. To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results. In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion. Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.",
keywords = "Cytosine deaminase, Head and neck neoplasms, Molecular targeted therapy, Neural stem cells, Tropism",
author = "Kwon, {Seong Keun} and Kim, {Seung U.} and Jae-Jun Song and Cho, {Chang Gun} and Park, {Seok Won}",
year = "2013",
month = "9",
day = "1",
doi = "10.3342/ceo.2013.6.3.176",
language = "English",
volume = "6",
pages = "176--183",
journal = "Clinical and Experimental Otorhinolaryngology",
issn = "1976-8710",
publisher = "Korean Society of Otolaryngology",
number = "3",

}

TY - JOUR

T1 - Selective delivery of a therapeutic gene for treatment of head and neck squamous cell carcinoma using human neural stem cells

AU - Kwon, Seong Keun

AU - Kim, Seung U.

AU - Song, Jae-Jun

AU - Cho, Chang Gun

AU - Park, Seok Won

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Objectives. Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods. To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results. In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion. Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

AB - Objectives. Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods. To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results. In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion. Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

KW - Cytosine deaminase

KW - Head and neck neoplasms

KW - Molecular targeted therapy

KW - Neural stem cells

KW - Tropism

UR - http://www.scopus.com/inward/record.url?scp=84884567248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884567248&partnerID=8YFLogxK

U2 - 10.3342/ceo.2013.6.3.176

DO - 10.3342/ceo.2013.6.3.176

M3 - Article

C2 - 24069522

AN - SCOPUS:84884567248

VL - 6

SP - 176

EP - 183

JO - Clinical and Experimental Otorhinolaryngology

JF - Clinical and Experimental Otorhinolaryngology

SN - 1976-8710

IS - 3

ER -