IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer.
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.
Wang
H
H
Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.
Yang
G
G
Timme
T L
TL
Fujita
T
T
Naruishi
K
K
Frolov
A
A
Brenner
M K
MK
Kadmon
D
D
Thompson
T C
TC
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D001859:Bone Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D004195:Disease Models, Animal; D015870:Gene Expression; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012190:Retroviridae / Q000235:genetics; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018664:Interleukin-12