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

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

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

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 THI-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.

Original languageEnglish (US)
Pages (from-to)8887-8896
Number of pages10
JournalCancer Research
Volume66
Issue number17
DOIs
StatePublished - Sep 1 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells'. Together they form a unique fingerprint.

  • Cite this