Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy

J. W. Choi, E. Kang, O. J. Kwon, T. J. Yun, H. K. Park, P. H. Kim, S. W. Kim, Jung-Hyun Kim, C. O. Yun

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

Original languageEnglish
Pages (from-to)880-892
Number of pages13
JournalGene Therapy
Volume20
Issue number9
DOIs
Publication statusPublished - 2013 Sep 1

Fingerprint

Adenoviridae
Gels
Injections
Neoplasms
alginic acid
Maintenance
Therapeutic Uses
Green Fluorescent Proteins
Heterografts
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Choi, J. W., Kang, E., Kwon, O. J., Yun, T. J., Park, H. K., Kim, P. H., ... Yun, C. O. (2013). Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy. Gene Therapy, 20(9), 880-892. https://doi.org/10.1038/gt.2013.10
Choi, J. W. ; Kang, E. ; Kwon, O. J. ; Yun, T. J. ; Park, H. K. ; Kim, P. H. ; Kim, S. W. ; Kim, Jung-Hyun ; Yun, C. O. / Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy. In: Gene Therapy. 2013 ; Vol. 20, No. 9. pp. 880-892.
@article{7e2e1a3d84ce427b9dbe6ee11def14e8,
title = "Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy",
abstract = "Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.",
author = "Choi, {J. W.} and E. Kang and Kwon, {O. J.} and Yun, {T. J.} and Park, {H. K.} and Kim, {P. H.} and Kim, {S. W.} and Jung-Hyun Kim and Yun, {C. O.}",
year = "2013",
month = "9",
day = "1",
doi = "10.1038/gt.2013.10",
language = "English",
volume = "20",
pages = "880--892",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "9",

}

Choi, JW, Kang, E, Kwon, OJ, Yun, TJ, Park, HK, Kim, PH, Kim, SW, Kim, J-H & Yun, CO 2013, 'Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy', Gene Therapy, vol. 20, no. 9, pp. 880-892. https://doi.org/10.1038/gt.2013.10

Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy. / Choi, J. W.; Kang, E.; Kwon, O. J.; Yun, T. J.; Park, H. K.; Kim, P. H.; Kim, S. W.; Kim, Jung-Hyun; Yun, C. O.

In: Gene Therapy, Vol. 20, No. 9, 01.09.2013, p. 880-892.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy

AU - Choi, J. W.

AU - Kang, E.

AU - Kwon, O. J.

AU - Yun, T. J.

AU - Park, H. K.

AU - Kim, P. H.

AU - Kim, S. W.

AU - Kim, Jung-Hyun

AU - Yun, C. O.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

AB - Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

UR - http://www.scopus.com/inward/record.url?scp=84883879888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883879888&partnerID=8YFLogxK

U2 - 10.1038/gt.2013.10

DO - 10.1038/gt.2013.10

M3 - Article

VL - 20

SP - 880

EP - 892

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 9

ER -