Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells

X. Zhang, P. Zhao, C. Kennedy, K. Chen, J. Wiegand, G. Washington, L. Marrero, Yan Cui

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor antigen-presenting DCs. These DCs subsequently stimulate marked and systemic immune activation. Here, we examined whether this level of immune activation is sufficient to overcome tumor-induced tolerogenic environment for treating an established aggressive epithelial tumor. We showed that a combination treatment of granulocyte macrophage-colony stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide stimulated large numbers of tumor antigen-presenting DCs in situ from transgene-modified stem cells. Moreover, these in situ generated and activated DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their numbers, as well as function, even in a tumor-bearing tolerogenic environment. This leads to significant improvement in the therapeutic efficacy of established pulmonary metastases. This study suggests that lentiviral vector-modified stem cells as DC progenitors may be used as an effective therapeutic regimen for treating metastatic epithelial tumors.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalCancer Gene Therapy
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Dendritic Cells
Stem Cells
Lung
Neoplasms
Antigen-Presenting Cells
Neoplasm Antigens
Therapeutics
Transgenes
CD8 Antigens
T-Lymphocytes
Active Immunotherapy
CD4 Antigens
Hematopoietic Stem Cell Transplantation
Cytosine
Guanine
Granulocyte-Macrophage Colony-Stimulating Factor
Oligonucleotides
Bone Marrow Cells
Phosphates
Neoplasm Metastasis

Keywords

  • Antigen-specific CTL function
  • Antitumor immunity
  • Dendritic cells
  • Hematopoietic stem cells
  • Lentiviral vector
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells. / Zhang, X.; Zhao, P.; Kennedy, C.; Chen, K.; Wiegand, J.; Washington, G.; Marrero, L.; Cui, Yan.

In: Cancer Gene Therapy, Vol. 15, No. 2, 01.02.2008, p. 73-84.

Research output: Contribution to journalArticle

Zhang, X, Zhao, P, Kennedy, C, Chen, K, Wiegand, J, Washington, G, Marrero, L & Cui, Y 2008, 'Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells', Cancer Gene Therapy, vol. 15, no. 2, pp. 73-84. https://doi.org/10.1038/sj.cgt.7701108
Zhang, X. ; Zhao, P. ; Kennedy, C. ; Chen, K. ; Wiegand, J. ; Washington, G. ; Marrero, L. ; Cui, Yan. / Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells. In: Cancer Gene Therapy. 2008 ; Vol. 15, No. 2. pp. 73-84.
@article{c1ccca65d6ee41cd9440e9130af7fa5e,
title = "Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells",
abstract = "Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor antigen-presenting DCs. These DCs subsequently stimulate marked and systemic immune activation. Here, we examined whether this level of immune activation is sufficient to overcome tumor-induced tolerogenic environment for treating an established aggressive epithelial tumor. We showed that a combination treatment of granulocyte macrophage-colony stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide stimulated large numbers of tumor antigen-presenting DCs in situ from transgene-modified stem cells. Moreover, these in situ generated and activated DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their numbers, as well as function, even in a tumor-bearing tolerogenic environment. This leads to significant improvement in the therapeutic efficacy of established pulmonary metastases. This study suggests that lentiviral vector-modified stem cells as DC progenitors may be used as an effective therapeutic regimen for treating metastatic epithelial tumors.",
keywords = "Antigen-specific CTL function, Antitumor immunity, Dendritic cells, Hematopoietic stem cells, Lentiviral vector, Renal cell carcinoma",
author = "X. Zhang and P. Zhao and C. Kennedy and K. Chen and J. Wiegand and G. Washington and L. Marrero and Yan Cui",
year = "2008",
month = "2",
day = "1",
doi = "10.1038/sj.cgt.7701108",
language = "English (US)",
volume = "15",
pages = "73--84",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells

AU - Zhang, X.

AU - Zhao, P.

AU - Kennedy, C.

AU - Chen, K.

AU - Wiegand, J.

AU - Washington, G.

AU - Marrero, L.

AU - Cui, Yan

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor antigen-presenting DCs. These DCs subsequently stimulate marked and systemic immune activation. Here, we examined whether this level of immune activation is sufficient to overcome tumor-induced tolerogenic environment for treating an established aggressive epithelial tumor. We showed that a combination treatment of granulocyte macrophage-colony stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide stimulated large numbers of tumor antigen-presenting DCs in situ from transgene-modified stem cells. Moreover, these in situ generated and activated DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their numbers, as well as function, even in a tumor-bearing tolerogenic environment. This leads to significant improvement in the therapeutic efficacy of established pulmonary metastases. This study suggests that lentiviral vector-modified stem cells as DC progenitors may be used as an effective therapeutic regimen for treating metastatic epithelial tumors.

AB - Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor antigen-presenting DCs. These DCs subsequently stimulate marked and systemic immune activation. Here, we examined whether this level of immune activation is sufficient to overcome tumor-induced tolerogenic environment for treating an established aggressive epithelial tumor. We showed that a combination treatment of granulocyte macrophage-colony stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide stimulated large numbers of tumor antigen-presenting DCs in situ from transgene-modified stem cells. Moreover, these in situ generated and activated DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their numbers, as well as function, even in a tumor-bearing tolerogenic environment. This leads to significant improvement in the therapeutic efficacy of established pulmonary metastases. This study suggests that lentiviral vector-modified stem cells as DC progenitors may be used as an effective therapeutic regimen for treating metastatic epithelial tumors.

KW - Antigen-specific CTL function

KW - Antitumor immunity

KW - Dendritic cells

KW - Hematopoietic stem cells

KW - Lentiviral vector

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=38349059202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349059202&partnerID=8YFLogxK

U2 - 10.1038/sj.cgt.7701108

DO - 10.1038/sj.cgt.7701108

M3 - Article

C2 - 18084244

AN - SCOPUS:38349059202

VL - 15

SP - 73

EP - 84

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 2

ER -