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A model for optimizing adenoviral delivery in human cancer gene therapy trials.

Publication ,  Journal Article
Barton, KN; Freytag, SO; Nurushev, T; Yoo, S; Lu, M; Yin, F-F; Li, S; Movsas, B; Kim, JH; Brown, SL
Published in: Hum Gene Ther
June 2007

Optimization of adenoviral delivery to the target volume is required for adenovirus-mediated cancer gene therapy to reach its maximal potential. The purpose of these studies was to develop a model of gene expression to improve adenovirus-mediated cancer gene therapy in the clinic. We measured the distribution of gene expression after a single deposit of a replication-competent adenovirus carrying the human sodium iodide symporter (hNIS) reporter gene was delivered to naive canine prostate and to human tumor xenografts. We generated hypothetical treatment plans for two prospective prostate cancer patients, using standard brachytherapy algorithms. In both models, the gene expression distribution from a single adenoviral deposit could be accurately described by a Gaussian function. In the naive canine prostate, a 0.1-ml deposit of 3 x 10(11) viral particles (VP) resulted in a gene expression volume of 1.14 +/- 0.70 cm(3), indicating that a minimum of 40 adenoviral deposits would be required to cover a 40-cm(3) prostate with therapeutic gene expression. On a viral particle basis, the gene expression volume obtained in human tumor xenografts (7 x 10(-12) cm(3)/VP) was twice that (3.5 x 10(-12) cm(3)/VP) measured in the naive canine prostate. Hypothetical treatment plans for two prostates indicated that 26 and 57 0.1-ml adenoviral deposits would be required to cover, respectively, 24- and 49-cm(3) prostates with gene expression. Although our studies focused on prostate, we believe the methodology to model gene expression presented here has much broader application to optimize treatment plans in other solid tumor sites; this assertion should be confirmed experimentally.

Duke Scholars

Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

June 2007

Volume

18

Issue

6

Start / End Page

562 / 572

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Symporters
  • Prostatic Neoplasms
  • Mice
  • Male
  • In Situ Hybridization
  • Humans
  • Genetic Vectors
  • Genetic Therapy
  • Dogs
 

Citation

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Barton, K. N., Freytag, S. O., Nurushev, T., Yoo, S., Lu, M., Yin, F.-F., … Brown, S. L. (2007). A model for optimizing adenoviral delivery in human cancer gene therapy trials. Hum Gene Ther, 18(6), 562–572. https://doi.org/10.1089/hum.2007.004
Barton, Kenneth N., Svend O. Freytag, Teamour Nurushev, Sua Yoo, Mei Lu, Fang-Fang Yin, Shidong Li, Benjamin Movsas, Jae Ho Kim, and Stephen L. Brown. “A model for optimizing adenoviral delivery in human cancer gene therapy trials.Hum Gene Ther 18, no. 6 (June 2007): 562–72. https://doi.org/10.1089/hum.2007.004.
Barton KN, Freytag SO, Nurushev T, Yoo S, Lu M, Yin F-F, et al. A model for optimizing adenoviral delivery in human cancer gene therapy trials. Hum Gene Ther. 2007 Jun;18(6):562–72.
Barton, Kenneth N., et al. “A model for optimizing adenoviral delivery in human cancer gene therapy trials.Hum Gene Ther, vol. 18, no. 6, June 2007, pp. 562–72. Pubmed, doi:10.1089/hum.2007.004.
Barton KN, Freytag SO, Nurushev T, Yoo S, Lu M, Yin F-F, Li S, Movsas B, Kim JH, Brown SL. A model for optimizing adenoviral delivery in human cancer gene therapy trials. Hum Gene Ther. 2007 Jun;18(6):562–572.
Journal cover image

Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

June 2007

Volume

18

Issue

6

Start / End Page

562 / 572

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Symporters
  • Prostatic Neoplasms
  • Mice
  • Male
  • In Situ Hybridization
  • Humans
  • Genetic Vectors
  • Genetic Therapy
  • Dogs