PMID- 16951206
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20210102
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 17
DP  - 2006 Sep 1
TI  - Induction of potent antitumor immunity by intratumoral injection of interleukin 
      23-transduced dendritic cells.
PG  - 8887-96
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a critical 
      role in priming immune responses to tumor. Interleukin (IL)-23 can act directly 
      on DC to promote immunogenic presentation of tumor peptide in vitro. Here, we 
      evaluated the combination of bone marrow-derived DC and IL-23 on the induction of 
      antitumor immunity in a mouse intracranial glioma model. DCs can be transduced by 
      an adenoviral vector coding single-chain mouse IL-23 to express high levels of 
      bioactive IL-23. Intratumoral implantation of IL-23-expressing DCs produced a 
      protective effect on intracranial tumor-bearing mice. The mice consequently 
      gained systemic immunity against the same tumor rechallenge. The protective 
      effect of IL-23-expressing DCs was comparable with or even better than that of 
      IL-12-expressing DCs. IL-23-transduced DC (DC-IL-23) treatment resulted in robust 
      intratumoral CD8(+) and CD4(+) T-cell infiltration and induced a specific 
      TH1-type response to the tumor in regional lymph nodes and spleen at levels 
      greater than those of nontransduced DCs. Moreover, splenocytes from animals 
      treated with DC-IL-23 showed heightened levels of specific CTL activity. In vivo 
      lymphocyte depletion experiments showed that the antitumor immunity induced by 
      DC-IL-23 was mainly dependent on CD8(+) T cells and that CD4(+) T cells and 
      natural killer cells were also involved. In summary, i.t. injection of DC-IL-23 
      resulted in significant and effective systemic antitumor immunity in intracranial 
      tumor-bearing mice. These findings suggest a new approach to induce potent 
      tumor-specific immunity to intracranial tumors. This approach may have 
      therapeutic potential for treating human glioma.
FAU - Hu, Jinwei
AU  - Hu J
AD  - Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, 
      CA 90048, USA.
FAU - Yuan, Xiangpeng
AU  - Yuan X
FAU - Belladonna, Maria L
AU  - Belladonna ML
FAU - Ong, John M
AU  - Ong JM
FAU - Wachsmann-Hogiu, Sebastian
AU  - Wachsmann-Hogiu S
FAU - Farkas, Daniel L
AU  - Farkas DL
FAU - Black, Keith L
AU  - Black KL
FAU - Yu, John S
AU  - Yu JS
LA  - eng
GR  - 1K23 NS02232/NS/NINDS NIH HHS/United States
GR  - 1R01 NS048959/NS/NINDS NIH HHS/United States
GR  - 1R21 NS048879/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Interleukin-23)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology/*transplantation
MH  - Glioma/*immunology
MH  - Interleukin-23/genetics/*immunology
MH  - Lymphocyte Depletion
MH  - Melanoma/*immunology
MH  - Mice
MH  - Neoplasms/*immunology
EDAT- 2006/09/05 09:00
MHDA- 2007/12/06 09:00
CRDT- 2006/09/05 09:00
PHST- 2006/09/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2006/09/05 09:00 [entrez]
AID - 66/17/8887 [pii]
AID - 10.1158/0008-5472.CAN-05-3448 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Sep 1;66(17):8887-96. doi: 10.1158/0008-5472.CAN-05-3448.