Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus.

Circulating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)-expressing conditionally replicating adenovirus (Ad) (rAd-GFP) was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells) when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus-adenovirus receptor (CAR) cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR.

Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis.

Autophagy is known to have a cytoprotective role under various cellular stresses; however, it also results in robust cell death as an important safeguard mechanism that protects the organism against invading pathogens and unwanted cancer cells. Autophagy is regulated by cell signalling including microRNA (miRNA), a post-transcriptional regulator of gene expression. Here, we show that genetically engineered telomerase-specific oncolytic adenovirus induced miR-7 expression, which is significantly associated with its cytopathic activity in human cancer cells.

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

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.

Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer.

A phase I dose-escalation study of telomerase-specific oncolytic adenovirus, OBP-301 (Telomelysin), is now under way in the United States to assess feasibility and to characterize its pharmacokinetics in patients with advanced solid tumors. The present preclinical study investigates whether OBP-301 and a chemotherapeutic agent that is commonly used for lung cancer treatment, gemcitabine, are able to enhance antitumor effects in vitro and in vivo. The antitumor effects of OBP-301 infection and gemcitabine were evaluated by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt assay.

Antiviral activity of cidofovir against telomerase-specific replication-selective oncolytic adenovirus, OBP-301 (Telomelysin).

We constructed a replication-competent oncolytic adenovirus, OBP-301 (Telomelysin), in which human telomerase reverse transcriptase (hTERT) promoter drives E1 genes. OBP-301 is currently being used in a phase-I clinical trial for various types of tumors. Under such conditions, anti-adenoviral agents should be available for safety use against OBP-301 since any adenoviral viremia could cause severe adverse effects.