The induction of antigen-specific CTL by in situ Ad-REIC gene therapy

Y. Ariyoshi, Masami Watanabe, S. Eikawa, Chihiro Yamazaki, T. Sadahira, T. Hirata, Motoo Araki, S. Ebara, Yasutomo Nasu, Heiichiro Udono, H. Kumon

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.Gene Therapy advance online publication, 25 February 2016; doi:10.1038/gt.2016.7.

Original languageEnglish
JournalGene Therapy
DOIs
Publication statusAccepted/In press - Feb 2 2016

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Cytotoxic T-Lymphocytes
Cell- and Tissue-Based Therapy
Genetic Therapy
Antigens
Ovalbumin
Neoplasm Antigens
Neoplasms
Cancer Vaccines
Dendritic Cells
Adenoviridae
Publications
Immunity
Spleen
Lymph Nodes
Apoptosis
Injections
Growth
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

The induction of antigen-specific CTL by in situ Ad-REIC gene therapy. / Ariyoshi, Y.; Watanabe, Masami; Eikawa, S.; Yamazaki, Chihiro; Sadahira, T.; Hirata, T.; Araki, Motoo; Ebara, S.; Nasu, Yasutomo; Udono, Heiichiro; Kumon, H.

In: Gene Therapy, 02.02.2016.

Research output: Contribution to journalArticle

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AU - Hirata, T.

AU - Araki, Motoo

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AU - Kumon, H.

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