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Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model

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Tumor Biology

Abstract

Due to the anatomical structure of the rectum, the treatment of rectal cancer remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1 promoter, can selectively replicate within and kill cancer cells derived from solid tumors. Thus, this virus provides a novel approach for the treatment of rectal cancer. Given the poor efficacy and possible adverse reactions that arise from the use of oncolytic virus alone and the results of our analysis of the efficacy of Ad-E2F in the treatment of rectal cancer, we investigated the use of oncolytic adenovirus in combination with adoptive immunotherapy using cytokine-induced killer (CIK) cells as a therapeutic treatment for rectal cancer. Our results illustrated that E2F-1 gene expression is higher in rectal cancer tissue than in normal tissue. Furthermore, the designed oncolytic adenovirus Ad-E2F is capable of selectively killing colorectal cell lines but has no significant effect on CIK cells. The results of in vitro and in vivo experiments demonstrated that combined therapy with Ad-E2F and CIK cells produce stronger antitumor effects than the administration of Ad-E2F or CIK cells alone. For low rectal cancers that are suitable for intratumoral injection, local injections of oncolytic viruses in combination with CIK cell-based adoptive immunotherapy may be suitable as a novel comprehensive therapeutic approach.

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Authors and Affiliations

  1. Institute of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China

    Yang Yan, Yingxin Xu, Yunshan Zhao, Li Li, Peiming Sun, Hailiang Liu, Qinghao Fan, Kai Liang, Wentao Liang, Huiwei Sun, Xiaohui Du & Rong Li

  2. General Surgery Department, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People’s Republic of China

    Xiaohui Du & Rong Li

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  1. Yang Yan
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  2. Yingxin Xu
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  11. Xiaohui Du
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Correspondence to Xiaohui Du or Rong Li.

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Figure S1

The phenotype of CIK cells. CIK cells from three healthy donors were stained with various antibodies as mentioned previously. The expressions of CD3, CD4, CD8, and CD56 were coincident with previously described results (JPEG 28 kb)

High resolution image (TIFF 1372 kb)

Figure S2

The effect of the adenoviral vectors on the proliferation of CIK cells. CIK cells were infected with Ad-E2F or Ad-EGFP, and the cell survival was measured by the MTT assay at different time points and different MOIs (JPEG 77 kb)

High resolution image (TIFF 90 kb)

Figure S3

The establishment of a BALB/c mouse model of orthotopic rectal cancer. Fourteen days after orthotopic injection, low rectal tumors were directly visible and confirmed by H&E staining (JPEG 114 kb)

High resolution image (TIFF 1045 kb)

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Yan, Y., Xu, Y., Zhao, Y. et al. Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model. Tumor Biol. 35, 1113–1122 (2014). https://doi.org/10.1007/s13277-013-1149-5

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  • DOI: https://doi.org/10.1007/s13277-013-1149-5

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