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Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.

Publication ,  Journal Article
Liu, X; Wu, J; Zhang, S; Li, C; Huang, Q
Published in: Cancer Gene Ther
November 2009

Immunotoxin therapy is a promising molecular cancer treatment strategy. Its main advantage is seletive cytotoxicity towards tumor cells and minimal toxicity in normal tissues. However, a short half-life and rapid clearance severely hampers its clinical application. We report here a novel genetic approach in which a recombinant adenovirus vector was used to deliver an immunotoxin gene e23(scFv)-PE40 targeted to the oncogene c-erbB-2 (also known as Her2/neu). This vector, when combined with a low dose of a conditionally replicative adenovirus vector (CRAd), has enhanced tumor-killing ability either alone or in combination with the chemotherapeutic agent etoposide. Our data show that low-dose CRAd facilitated the replication of replication-deficient Ad-e23(scFv)-PE40 up to 6-20 times and the transcription of e23(scFv)-PE40 gene up to 12 times. Moreover, etoposide increased the e23(scFv)-PE40 transcription up to 8.5 times. Furthermore, we show that systemic application of Ad-e23(scFv)-PE40 and enhanced expression of the immunotoxin gene was well tolerated as determined by serum biochemical markers and histological examination of most vital organs. Taken together, our data support a novel genetic immunotoxin delivery approach that may yield enhanced efficacy against a variety of Her2/neu-expressing tumors.

Duke Scholars

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Published In

Cancer Gene Ther

DOI

EISSN

1476-5500

Publication Date

November 2009

Volume

16

Issue

11

Start / End Page

861 / 872

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Virulence Factors
  • Pseudomonas aeruginosa Exotoxin A
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Immunotoxins
 

Citation

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Liu, X., Wu, J., Zhang, S., Li, C., & Huang, Q. (2009). Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy. Cancer Gene Ther, 16(11), 861–872. https://doi.org/10.1038/cgt.2009.30
Liu, X., J. Wu, S. Zhang, C. Li, and Q. Huang. “Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.Cancer Gene Ther 16, no. 11 (November 2009): 861–72. https://doi.org/10.1038/cgt.2009.30.
Liu X, Wu J, Zhang S, Li C, Huang Q. Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy. Cancer Gene Ther. 2009 Nov;16(11):861–72.
Liu, X., et al. “Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy.Cancer Gene Ther, vol. 16, no. 11, Nov. 2009, pp. 861–72. Pubmed, doi:10.1038/cgt.2009.30.
Liu X, Wu J, Zhang S, Li C, Huang Q. Novel strategies to augment genetically delivered immunotoxin molecular therapy for cancer therapy. Cancer Gene Ther. 2009 Nov;16(11):861–872.

Published In

Cancer Gene Ther

DOI

EISSN

1476-5500

Publication Date

November 2009

Volume

16

Issue

11

Start / End Page

861 / 872

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Virulence Factors
  • Pseudomonas aeruginosa Exotoxin A
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Immunotoxins