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Coagulation factors determine tumor transduction in vivo

Marta Gimenez-Alejandre1, Manel Cascallo, Neus Bayo-Puxan

  • 1Translational Research Laboratory, Institut d'Investigació Biomèdica de Bellvitge-Institut Català d'Oncologia, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.

Human Gene Therapy
|September 18, 2008
PubMed

Insights

Adenoviruses target tumors via blood coagulation factors, not direct cell interaction. Eliminating these factors stops tumor transduction, presenting challenges for gene therapy targeting.

Area of Science:

  • Oncology
  • Virology
  • Gene Therapy

Background:

  • Adenoviral vectors are crucial for cancer gene therapy and virotherapy.
  • Targeting tumor cells effectively in vivo remains a significant challenge.
  • Adenovirus type 5 typically infects epithelial cells via CAR and integrins, but blood-borne infections differ.

Purpose of the Study:

  • To investigate if blood-borne adenoviruses infect tumor cells in vivo via a pathway involving blood coagulation factors.
  • To determine the role of coagulation factors in tumor cell transduction by adenoviruses.

Main Methods:

  • In vitro and in vivo analyses were conducted.
  • Experiments involved studying adenovirus transduction in the presence and absence of vitamin K-dependent coagulation factors.

Main Results:

  • Vitamin K-dependent coagulation zymogens were found to mediate tumor transduction.
  • Elimination of these coagulation factors abrogated adenovirus-mediated tumor transduction.
  • This suggests an indirect infection pathway for adenoviruses in tumors.

Conclusions:

  • Adenoviruses utilize blood coagulation factors for infecting tumor cells in vivo.
  • This indirect pathway presents novel challenges for retargeting adenoviruses in cancer therapy.
  • Understanding this mechanism is critical for developing more effective adenoviral-based cancer treatments.

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