In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 298-298
Abstract:
Interleukin (IL)-12 has been shown to be one of the most promising antitumor cytokines. The major antitumor activities of IL-12 rely on its ability to promote T helper type 1 (Th1) immune responses and CTL responses. However, immune suppression-dominated microenvironments in advanced tumors hinder the effect of IL-12 gene therapy for cancer. Most tumor cells produce large amounts of transforming growth factor-β (TGF-β), which plays crucial roles of tumor-induced immune suppression. The TGF-β inhibits proliferation of immune cells such as T, NK, and dendritic cells, resulting in suppression of antitumor immunity. Moreover, TGF-β is also known to regulate the maintenance and induction of regulatory T (Treg) cells. Thus, it has been hypothesized that inhibiting TGF-β might be an apt strategy for generating more effective cancer immunotherapy. Therefore, to enhance the efficiency of IL-12-mediated cancer immunotherapy, we generated oncolytic adenovirus co-expressing IL-12 and Decorin (hDCN) (RdB/IL12/hDCN) as suitable therapeutic adjuvant to overcome immune suppression by down-regulation of TGF-β through hDCN. Intratumoral administration of RdB/IL12/hDCN promoted enhanced antitumor effects compared with an oncolytic adenovirus expressing IL-12 or hDCN alone (RdB/IL12 or RdB/hDCN, respectively). We showed markedly elevated levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α and IFN-γ secreting cells in RdB/IL12/hDCN-treated tumors. Moreover, Treg in draining lymph nodes (DLNs) dramatically decreased in mice treated with RdB/IL12/hDCN, suggesting an association with the down-regulation of TGF-β in tumor treated with RdB/IL12/hDCN. Consistent with these data, tumor tissue injected with RdB/IL12/hDCN showed increased infiltration of CD4+ T and CD8+ T cells infiltration. Furthermore, hDCN enhanced viral distribution and tumor penetration, leading to improved virus-mediated cancer gene therapy by overcoming the extracellular matrix barrier within tumor masses. Together, these results provide new insight into the ability of hDCN to eliminate immune suppression and demonstrate that adenovirus co-expressing IL-12 and hDCN is a promising therapeutic tool for cancer treatment than adenovirus expressing IL-12 alone. Note: This abstract was not presented at the meeting. Citation Format: Eonju Oh, Il-Kyu Choi, June Kyu Hwang, Chae-Ok Yun. Overcoming TGF-β-related immunosuppression for cancer immunotherapy by oncolytic adenovirus co-expressing Interleukin-12 and decorin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 298. doi:10.1158/1538-7445.AM2015-298
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-298
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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