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 language | English |
|---|---|
| Pages (from-to) | 7853-7860 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 22 |
| Publication status | Published - Nov 15 2003 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model
AU - Satoh, Takefumi
AU - Saika, Takashi
AU - Ebara, Shin
AU - Kusaka, Nobuyuki
AU - Timme, Terry L.
AU - Yang, Guang
AU - Wang, Jianxiang
AU - Mouraviev, Vladimir
AU - Cao, Guangwen
AU - Fattah, El Moataz Abdel
AU - Thompson, Timothy C.
PY - 2003/11/15
Y1 - 2003/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10744228469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744228469&partnerID=8YFLogxK
M3 - Article
C2 - 14633713
AN - SCOPUS:10744228469
VL - 63
SP - 7853
EP - 7860
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 22
ER -