Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model

K. Tabata, S. Kurosaka, Masami Watanabe, Kohei Edamura, T. Satoh, G. Yang, E. Abdelfattah, J. Wang, A. Goltsov, D. Floryk, T. C. Thompson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously identified the mouse and human Glipr1 and GLIPR1/RTVP-1 genes, respectively, as direct p53 targets with proapoptotic activities in various cancer cell lines, including prostate cancer (PCa). Intratumoral injection of an adenoviral vector capable of efficient transduction and expression of Glipr1 (AdGlipr1) yielded promising therapeutic results in an orthotopic, metastatic mouse model of PCa. AdGlipr1-transduced macrophages (M/Glipr1) generated greater surface expression of CD40, CD80 and major histocompatibility complex class II molecules and greater production of interleukin 12 (IL-12) and IL-6 in vitro than control macrophages did. Mechanistic analysis indicated that increased production of IL-12 in M/Glipr1 depends on activation of the p38 signaling cascade. M/Glipr1 injected into orthotopic 178-2BMA tumors in vivo resulted in significantly suppressed prostate tumor growth and spontaneous lung metastases and longer survival relative to those observed in control-treated mice. Furthermore, these preclinical data indicate the generation of systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses. Trafficking studies confirmed that intratumorally injected M/Glipr1 could migrate to draining lymph nodes. Overall, our data suggest that this novel gene-modified cell approach is an effective treatment avenue that induces antitumor immune responses in preclinical studies.

Original languageEnglish
Pages (from-to)969-978
Number of pages10
JournalGene Therapy
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Macrophages
Neoplasm Metastasis
Interleukin-12
Growth
Genes
Neoplasms
Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
Natural Killer Cells
Prostate
Interleukin-6
Lymph Nodes
Cell Line
Lung
Injections
Survival
Therapeutics

Keywords

  • gene-modified cell therapy
  • Glipr1
  • macrophages
  • prostate cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model. / Tabata, K.; Kurosaka, S.; Watanabe, Masami; Edamura, Kohei; Satoh, T.; Yang, G.; Abdelfattah, E.; Wang, J.; Goltsov, A.; Floryk, D.; Thompson, T. C.

In: Gene Therapy, Vol. 18, No. 10, 10.2011, p. 969-978.

Research output: Contribution to journalArticle

Tabata, K, Kurosaka, S, Watanabe, M, Edamura, K, Satoh, T, Yang, G, Abdelfattah, E, Wang, J, Goltsov, A, Floryk, D & Thompson, TC 2011, 'Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model', Gene Therapy, vol. 18, no. 10, pp. 969-978. https://doi.org/10.1038/gt.2011.51
Tabata, K. ; Kurosaka, S. ; Watanabe, Masami ; Edamura, Kohei ; Satoh, T. ; Yang, G. ; Abdelfattah, E. ; Wang, J. ; Goltsov, A. ; Floryk, D. ; Thompson, T. C. / Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model. In: Gene Therapy. 2011 ; Vol. 18, No. 10. pp. 969-978.
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