Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model.

Abstract

BACKGROUND:

Although cancer therapy using replication-selective oncolytic adenoviruses has been available for many years, its anti-tumor efficacy is suboptimal as a result of low and nonspecific infectivity that depends on coxsackie adenovirus receptor expression of the target cancer and normal cells, and generation of an anti-adenovirus neutralizing antibody. In addition, concerns of triggering a severe innate immune response against the adenovirus limit the systemic administration. We developed the carrier cell-based oncolytic virus system (CBOVS) using irradiated tumor cells as carrier cells and concealing the adenovirus (Ad-IAI.3B) inside to improve the specific infectivity. We investigated the anti-tumor effect of CBOVS in a multiple lung tumor mouse model.

METHODS:

The ability of CBOVS to infect Ad-IAI.3B to the target cancer cells was examined in vitro in the presence of anti-adenovirus antibodies. To evaluate the systemic effect of CBOVS, we intravenously injected CBOVS into mice with lung tumors (KLN205 cell lines).

RESULTS:

CBOVS enhanced the infectivity of Ad-IAI.3B to tumor cells in the presence of anti-adenovirus antibodies in vitro. Intravenous injections of CBOVS produced an accumulation of the adenovirus in the lung-bearing tumors and produced a strong anti-tumor effect in vivo. Furthermore, lymphocytes collected from the CBOVS-treated mice induced an increase in cytokines related to the Th1 response (interferon-γ, interleukin-12) by pulsing with KLN205.

CONCLUSIONS:

These findings suggest that CBOVS could protect adenoviruses from neutralizing antibodies and systemically deliver them to lung tumors. Furthermore, CBOVS appears to have potential as a tumor cell vaccine that activates cytotoxic immunity against cancer cells.

• Authors: Aya Saito, Naoya Morishita, Chihomi Mitsuoka, Shunichi Kitajima, Katsuyuki Hamada, Kyung-Mi Lee, Masato Kawabata, Masato Fujisawa, Toshiro Shirakawa
• Journal: The journal of gene medicine (J Gene Med) Vol. 13 Issue 6 Pg. 353-61 (Jun 2011) ISSN: 1521-2254 [Electronic] England
• PMID: 21674738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Cancer Vaccines
• Cytokines
• DNA Primers

Topics

• Adenoviridae (genetics, immunology)
• Animals
• Cancer Vaccines (administration & dosage, genetics, therapeutic use)
• Carcinoma, Squamous Cell (immunology, prevention & control)
• Cell Culture Techniques
• Cytokines (immunology)
• DNA Primers (genetics)
• Genetic Therapy (methods)
• Immunohistochemistry
• Lung Neoplasms (immunology, prevention & control)
• Mice
• Oncolytic Viruses (genetics, immunology)
• Reverse Transcriptase Polymerase Chain Reaction