Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model

Takefumi Satoh, Takashi Saika, Shin Ebara, Nobuyuki Kusaka, Terry L. Timme, Guang Yang, Jianxiang Wang, Vladimir Mouraviev, Guangwen Cao, El Moataz Abdel Fattah, Timothy C. Thompson

Research output: Contribution to journalArticle

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Abstract

We investigated the efficacy of intratumoral injection of macrophages transduced with murine IL-12 recombinant adenoviral vector (AdmIL-12) using the orthotopic 178-2 BMA mouse prostate cancer model. AdmIL-12-transduced macrophages secreted IL-12 in vitro and demonstrated increased surface expression of MHC classes I and II as well as F4/80 antigen compared with uninfected macrophages or those infected with an adenoviral vector containing β-galactosidase (Adβgal) in control macrophages. AdmIL-12-transduced macrophages injected into orthotopic 178-2 BMA tumors in vivo induced significant suppression of primary tumor growth and spontaneous lung metastases compared with controls. These antitumor and antimetastatic effects were comparable with those resulting from direct orthotopic delivery of the AdmIL-12 vector. Mice with orthotopic tumors treated with AdmIL-12-transduced macrophages survived significantly longer than controls. Analysis of tumors demonstrated significantly increased infiltration of CD4+ and CD8+ T cells in those injected with AdmIL-12-transduced macrophages compared with controls. Splenocyte-derived cytotoxic natural killer cell activity was enhanced on day 2 after AdmIL-12-transduced macrophage injection, and on day 14, tumor-specific T-lymphocyte activities were increased compared with control, Adβgal-infected macrophages. Trafficking studies confirmed that intratumorally injected, AdmIL-12-transduced macrophages could migrate to draining lymph nodes. Overall, this novel approach to prostate cancer therapy demonstrates antitumor immune responses that provide effective antimetastatic activities in preclinical studies.

Original languageEnglish
Pages (from-to)7853-7860
Number of pages8
JournalCancer Research
Volume63
Issue number22
Publication statusPublished - Nov 15 2003
Externally publishedYes

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Interleukin-12
Prostatic Neoplasms
Macrophages
Neoplasm Metastasis
Growth
Neoplasms
Galactosidases
T-Lymphocytes
Injections
Natural Killer Cells
Lymph Nodes
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Satoh, T., Saika, T., Ebara, S., Kusaka, N., Timme, T. L., Yang, G., ... Thompson, T. C. (2003). Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model. Cancer Research, 63(22), 7853-7860.

Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model. / Satoh, Takefumi; Saika, Takashi; Ebara, Shin; Kusaka, Nobuyuki; Timme, Terry L.; Yang, Guang; Wang, Jianxiang; Mouraviev, Vladimir; Cao, Guangwen; Fattah, El Moataz Abdel; Thompson, Timothy C.

In: Cancer Research, Vol. 63, No. 22, 15.11.2003, p. 7853-7860.

Research output: Contribution to journalArticle

Satoh, T, Saika, T, Ebara, S, Kusaka, N, Timme, TL, Yang, G, Wang, J, Mouraviev, V, Cao, G, Fattah, EMA & Thompson, TC 2003, 'Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model', Cancer Research, vol. 63, no. 22, pp. 7853-7860.
Satoh, Takefumi ; Saika, Takashi ; Ebara, Shin ; Kusaka, Nobuyuki ; Timme, Terry L. ; Yang, Guang ; Wang, Jianxiang ; Mouraviev, Vladimir ; Cao, Guangwen ; Fattah, El Moataz Abdel ; Thompson, Timothy C. / Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model. In: Cancer Research. 2003 ; Vol. 63, No. 22. pp. 7853-7860.
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