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 journalArticlepeer-review

12 Scopus citations

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 2008

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

Fingerprint Dive into the research topics of 'Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells'. Together they form a unique fingerprint.

Cite this