In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy

Toru Kojima, Yuichi Watanabe, Yuuri Hashimoto, Shinji Kuroda, Yasumoto Yamasaki, Shuuya Yano, Masaaki Ouchi, Hiroshi Tazawa, Futoshi Uno, Shunsuke Kagawa, Satoru Kyo, Hiroyuki Mizuguchi, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background/Objective: The aim of this study was to develop a less invasive way of targeting lymph node metastasis for the treatment of human gastrointestinal cancer. Lymphatic invasion is a major route for cancer cell dissemination, and adequate treatment of locoregional lymph nodes is required for curative treatment in patients with malignancies. Methods: Human telomerase reverse transcription (hTERT) is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. OBP-301 (Telomelysin) is an attenuated adenovirus with oncolytic potency that contains the hTERT promoter element to regulate viral replication. We examined whether OBP-301 injected into the primary tumor might be useful for purging micrometastasis from regional lymph nodes in an orthotopic colorectal cancer model. Results: OBP-301 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice. By using a highly sensitive quantitative PCR analysis that targets the human-specific Alu sequence, we showed that OBP-301 caused viral spread into the regional lymphatic area and selectively replicated in neoplastic lesions, resulting in tumor-cell-specific death in metastatic lymph nodes. Moreover, although the surgical removal of primary tumors increased the tendency of lymph node metastasis, preoperative intratumoral injection of virus significantly reduced lymph node metastasis. Conclusions: Our results indicate that intratumoral injection of OBP-301 mediates effective in vivo purging of metastatic tumor cells from regional lymph nodes, which may help optimize treatment of human cancer, especially gastrointestinal malignancies.

Original languageEnglish
Pages (from-to)1079-1086
Number of pages8
JournalAnnals of Surgery
Volume251
Issue number6
DOIs
Publication statusPublished - Jun 2010

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Oncolytic Virotherapy
Telomerase
Colorectal Neoplasms
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Gastrointestinal Neoplasms
Reverse Transcription
Neoplasm Micrometastasis
Injections
Therapeutics
Rectum
Adenoviridae
Cell Death

ASJC Scopus subject areas

  • Surgery

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In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy. / Kojima, Toru; Watanabe, Yuichi; Hashimoto, Yuuri; Kuroda, Shinji; Yamasaki, Yasumoto; Yano, Shuuya; Ouchi, Masaaki; Tazawa, Hiroshi; Uno, Futoshi; Kagawa, Shunsuke; Kyo, Satoru; Mizuguchi, Hiroyuki; Urata, Yasuo; Tanaka, Noriaki; Fujiwara, Toshiyoshi.

In: Annals of Surgery, Vol. 251, No. 6, 06.2010, p. 1079-1086.

Research output: Contribution to journalArticle

Kojima, Toru ; Watanabe, Yuichi ; Hashimoto, Yuuri ; Kuroda, Shinji ; Yamasaki, Yasumoto ; Yano, Shuuya ; Ouchi, Masaaki ; Tazawa, Hiroshi ; Uno, Futoshi ; Kagawa, Shunsuke ; Kyo, Satoru ; Mizuguchi, Hiroyuki ; Urata, Yasuo ; Tanaka, Noriaki ; Fujiwara, Toshiyoshi. / In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy. In: Annals of Surgery. 2010 ; Vol. 251, No. 6. pp. 1079-1086.
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AU - Kojima, Toru

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AU - Hashimoto, Yuuri

AU - Kuroda, Shinji

AU - Yamasaki, Yasumoto

AU - Yano, Shuuya

AU - Ouchi, Masaaki

AU - Tazawa, Hiroshi

AU - Uno, Futoshi

AU - Kagawa, Shunsuke

AU - Kyo, Satoru

AU - Mizuguchi, Hiroyuki

AU - Urata, Yasuo

AU - Tanaka, Noriaki

AU - Fujiwara, Toshiyoshi

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