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Induction of Potent Antitumor Immunity by Intratumoral Injection of Interleukin 23–Transduced Dendritic Cells

¹ Maxine Dunitz Neurosurgical Institute and ² Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California and ³ Department of Experimental Medicine, University of Perugia, Perugia, Italy

Requests for reprints: John S. Yu, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Suite 800 East, 8631 West 3rd Street, Los Angeles, CA 90048. Phone: 310-423-0845; Fax: 310-423-0810; E-mail: yuj{at}cshs.org.

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. (Cancer Res 2006; 66(17): 8887-96)

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