RRC ID |
12164
|
著者 |
Furumoto K, Arii S, Yamasaki S, Mizumoto M, Mori A, Inoue N, Isobe N, Imamura M.
|
タイトル |
Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.
|
ジャーナル |
Int J Cancer
|
Abstract |
The major goal in cancer immunotherapy is the induction of tumor-specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a murine tumor model to examine whether spleen-derived DCs transduced with the IL-12 gene could elicit tumor-specific immune responses. BALB/c mice injected peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed DCs inhibited the growth of day 5-established subcutaneous CT26 tumors. Splenocytes from treated mice responded specifically to parental tumor cells and showed increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T-lymphocyte (CTL) activity. Increased numbers of both CD4(+) and CD8(+) T cells were detected in the treated tumors. The inhibition of tumor growth was significantly greater in mice injected with IL-12 gene-transduced DCs than in those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding adenovirus itself. Taken together, these results indicate that DCs transduced with the IL-12 gene by a recombinant adenovirus are effective in inducing tumor-specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors.
|
巻・号 |
87(5)
|
ページ |
665-72
|
公開日 |
2000-9-1
|
PII |
10.1002/1097-0215(20000901)87:5<665::AID-IJC8>3.0.CO;2-F
|
PMID |
10925360
|
MeSH |
Adenocarcinoma / immunology
Adenocarcinoma / pathology
Adenocarcinoma / therapy
Adenoviridae / genetics
Animals
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Cell Division / physiology
Colonic Neoplasms / immunology
Colonic Neoplasms / pathology
Colonic Neoplasms / therapy
Dendritic Cells / immunology*
Dendritic Cells / physiology
Fibroblasts / physiology
Humans
Immunotherapy, Adoptive*
Interferon-gamma / biosynthesis
Interferon-gamma / immunology
Interleukin-12 / biosynthesis*
Interleukin-12 / genetics*
Interleukin-12 / immunology
Interleukin-4 / biosynthesis
Interleukin-4 / immunology
Lymphocyte Activation / immunology
Lymphocytes, Tumor-Infiltrating / immunology
Male
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Spleen / cytology
Spleen / immunology
T-Lymphocytes, Cytotoxic / immunology
Th1 Cells / immunology
Th1 Cells / metabolism
Transduction, Genetic
|
IF |
5.145
|
引用数 |
42
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
遺伝子材料 |
AxCAmIL12p40 Adex1CAmIL12p40 (RDB1417) AxCAmIL12p35 Adex1CAmIL12p35 (RDB1414) |