Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells.

Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Research Abstract Details 

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Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Abstract Text:

Jinwei Hu,Xiangpeng Yuan,Maria L Belladonna,John M Ong,Sebastian Wachsmann-Hogiu,Daniel L Farkas,Keith L Black,John S Yu,

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.

Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Publishing Authors By Initials

J Hu,X Yuan,ML Belladonna,JM Ong,S Wachsmann-Hogiu,DL Farkas,KL Black,JS Yu,

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Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 66

Page Numbers: 8887-96

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ISSN: 1538-7445

DAY: 1

MONTH: Sep

YEAR: 2006

Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells.

AFFILIATION: Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Country: United States

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MEDLINETA: Cancer Res

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