Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells.
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.
Hu
Jinwei
J
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Yuan
Xiangpeng
X
Belladonna
Maria L
ML
Ong
John M
JM
Wachsmann-Hogiu
Sebastian
S
Farkas
Daniel L
DL
Black
Keith L
KL
Yu
John S
JS
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005910:Glioma / Q000276:immunology*; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology*
D053759:Interleukin-23