IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer

H. Wang; G. Yang; T. L. Timme; T. Fujita; K. Naruishi; A. Frolov; Malcolm Brenner; D. Kadmon; T. C. Thompson

doi:10.1038/sj.cgt.7701069

IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer

H. Wang, G. Yang, T. L. Timme, T. Fujita, K. Naruishi, A. Frolov, Malcolm Brenner, D. Kadmon, T. C. Thompson

Houston Methodist

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.

Original language	English (US)
Pages (from-to)	819-827
Number of pages	9
Journal	Cancer Gene Therapy
Volume	14
Issue number	10
DOIs	https://doi.org/10.1038/sj.cgt.7701069
State	Published - Oct 2007

Keywords

Bone marrow cells
Cancer vaccination
Gene therapy
IL-12
Metastasis

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cancer Research

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title = "IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer",

abstract = "To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.",

keywords = "Bone marrow cells, Cancer vaccination, Gene therapy, IL-12, Metastasis",

author = "H. Wang and G. Yang and Timme, {T. L.} and T. Fujita and K. Naruishi and A. Frolov and Malcolm Brenner and D. Kadmon and Thompson, {T. C.}",

note = "Funding Information: This work was supported by a grant from the National Cancer Institute (Specialized Program or Research Excellence, SPORE P50-58204).",

year = "2007",

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doi = "10.1038/sj.cgt.7701069",

language = "English (US)",

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AU - Wang, H.

AU - Yang, G.

AU - Timme, T. L.

AU - Fujita, T.

AU - Naruishi, K.

AU - Frolov, A.

AU - Brenner, Malcolm

AU - Kadmon, D.

AU - Thompson, T. C.

N1 - Funding Information: This work was supported by a grant from the National Cancer Institute (Specialized Program or Research Excellence, SPORE P50-58204).

PY - 2007/10

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N2 - To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.

AB - To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.

KW - Bone marrow cells

KW - Cancer vaccination

KW - Gene therapy

KW - IL-12

KW - Metastasis

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IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer

Abstract

Keywords

ASJC Scopus subject areas

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