2005 Fiscal Year Final Research Report Summary
Development of cell and gene therapy for prostate cancer with dendritic cells engineered to produce interleukin-12
| Project/Area Number |
16591596
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
SAIKA Takashi Okayama University, University Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (10314676)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NASU Yasutomo Okayama University, Graduate School of Medicine, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237572)
MANABE Daisuke Okayama University, University Hospital of Medicine and Dentistry, Senior resident, 医学部・歯学部附属病院, 医員 (90379793)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Dendritic cell / Gene therapy / cancer immunology / Interleukin-12 / Prostate Cancer |
|---|
| Research Abstract |
Bone marrow-derived DC were genetically engineered to express high levels of interleukin-12 (IL-12) with or without the costimulatory molecule B7-1, by ex vivo infection with recombinant adenoviral vectors. We used an orthotopic metastatic mouse prostate cancer preclinical model to compare two therapeutic protocols for DC delivery, in situ and subcutaneous. In vitro DC/IL-12 or DC/IL-12/B7 produced high levels of biologically active IL-12. In situ delivery of DC/IL-12 or DC/IL-12/B7 induced a significant suppression of primary tumor growth compared to DC/beta gal controls, as well as reduced numbers of spontaneous lung metastatic nodules. In survival experiments, in situ DC/IL-12 injection demonstrated a significant advantage. Subcutaneous, tumor lysate pulsed DC/IL-12 significantly decreased tumor size and increased survival compared to HBSS controls but the decrease in the number of spontaneous lung metastases did not achieve statistical significance. Both in situ and subcutaneous treatments enhanced cytolytic activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In this preclinical model, gene-modified DC-based intratumoral immunotherapy was shown to be an effective therapeutic strategy for locally advanced prostate cancer based on tumor growth suppression, inhibition of metastasis and survival improvement.
|
