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

Aya Saito, Naoya Morishita, Chihomi Mitsuoka, Shunichi Kitajima, Katsuyuki Hamada, Kyung-Mi Lee, Masato Kawabata, Masato Fujisawa, Toshiro Shirakawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalJournal of Gene Medicine
Volume13
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

Fingerprint

Cancer Vaccines
Adenoviridae
Intravenous Injections
Squamous Cell Carcinoma
Oncolytic Viruses
Lung
Growth
Neoplasms
Neutralizing Antibodies
Anti-Idiotypic Antibodies
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Interleukin-12

Keywords

  • Adenovirus
  • Carrier cell
  • Gene therapy
  • Immune therapy
  • Squamous cell carcinoma
  • Tumor cell vaccine

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

Cite this

Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model. / Saito, Aya; Morishita, Naoya; Mitsuoka, Chihomi; Kitajima, Shunichi; Hamada, Katsuyuki; Lee, Kyung-Mi; Kawabata, Masato; Fujisawa, Masato; Shirakawa, Toshiro.

In: Journal of Gene Medicine, Vol. 13, No. 6, 01.06.2011, p. 353-361.

Research output: Contribution to journalArticle

Saito, Aya ; Morishita, Naoya ; Mitsuoka, Chihomi ; Kitajima, Shunichi ; Hamada, Katsuyuki ; Lee, Kyung-Mi ; Kawabata, Masato ; Fujisawa, Masato ; Shirakawa, Toshiro. / Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model. In: Journal of Gene Medicine. 2011 ; Vol. 13, No. 6. pp. 353-361.
@article{91ad7fb8b1024dd48df78caacc15f422,
title = "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.",
keywords = "Adenovirus, Carrier cell, Gene therapy, Immune therapy, Squamous cell carcinoma, Tumor cell vaccine",
author = "Aya Saito and Naoya Morishita and Chihomi Mitsuoka and Shunichi Kitajima and Katsuyuki Hamada and Kyung-Mi Lee and Masato Kawabata and Masato Fujisawa and Toshiro Shirakawa",
year = "2011",
month = "6",
day = "1",
doi = "10.1002/jgm.1578",
language = "English",
volume = "13",
pages = "353--361",
journal = "Journal of Gene Medicine",
issn = "1099-498X",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model

AU - Saito, Aya

AU - Morishita, Naoya

AU - Mitsuoka, Chihomi

AU - Kitajima, Shunichi

AU - Hamada, Katsuyuki

AU - Lee, Kyung-Mi

AU - Kawabata, Masato

AU - Fujisawa, Masato

AU - Shirakawa, Toshiro

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

KW - Adenovirus

KW - Carrier cell

KW - Gene therapy

KW - Immune therapy

KW - Squamous cell carcinoma

KW - Tumor cell vaccine

UR - http://www.scopus.com/inward/record.url?scp=79959730726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959730726&partnerID=8YFLogxK

U2 - 10.1002/jgm.1578

DO - 10.1002/jgm.1578

M3 - Article

VL - 13

SP - 353

EP - 361

JO - Journal of Gene Medicine

JF - Journal of Gene Medicine

SN - 1099-498X

IS - 6

ER -