Self-deleting suicide vectors (SDSV): selective killing of p53-deficient cancer cells

T Andreú1, C Ebensperger, E M Westphal

  • 1Laboratory for Molecular Hematology, Department of Hematology, University of Frankfurt Medical School, 60596 Frankfurt, Germany.

Cancer Research
|September 18, 2001
PubMed

Insights

A novel retrovirus vector selectively targets cancer cells with faulty p53 tumor suppressor protein. This vector deletes itself from healthy cells but enables cancer cell killing via ganciclovir treatment in non-functional p53 cells.

Area of Science:

  • * Molecular Biology
  • * Virology
  • * Cancer Therapeutics

Background:

  • * Cancer cells often harbor dysfunctional p53 tumor suppressor proteins.
  • * Selective cancer cell targeting remains a challenge in oncology.

Purpose of the Study:

  • * To develop a self-deleting retrovirus vector for selective cancer cell elimination.
  • * To exploit the p53 tumor suppressor protein status for targeted therapy.

Main Methods:

  • * Construction of a self-deleting retrovirus vector encoding the herpes simplex virus (HSV)-thymidine kinase suicide gene.
  • * Utilization of Cre/loxP site-specific recombination for provirus deletion.
  • * Testing in cancer cells with functional, non-functional, or mutant p53.

Main Results:

  • * Functional p53 cells successfully deleted the integrated provirus and HSV-thymidine kinase gene.
  • * Cells lacking functional p53 or expressing a mutant form retained the provirus.
  • * Retained provirus rendered cancer cells susceptible to ganciclovir-induced cell death.

Conclusions:

  • * The developed retrovirus vector offers a novel strategy for selective cancer cell killing.
  • * This approach can be adapted for targeting tumors with various dysfunctional transcription factors.

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