RRC ID 12164
Author Furumoto K, Arii S, Yamasaki S, Mizumoto M, Mori A, Inoue N, Isobe N, Imamura M.
Title Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.
Journal 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.
Volume 87(5)
Pages 665-72
Published 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 7.36
Times Cited 38
DNA material AxCAmIL12p40 Adex1CAmIL12p40 (RDB1417) AxCAmIL12p35 Adex1CAmIL12p35 (RDB1414)