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Tumor antigen LRRC15 impedes adenoviral infection: implications for virus-based cancer therapy

Jim O'Prey1, Simon Wilkinson, Kevin M Ryan

  • 1Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, United Kingdom.

Journal of Virology
|April 4, 2008
PubMed

Insights

Adenovirus-delivered p53 therapy is hindered by LRRC15, a tumor antigen that blocks viral entry. This finding impacts the development of adenovirus-based cancer treatments.

Area of Science:

  • Oncolytic virotherapy
  • Cancer biology
  • Viral immunology

Background:

  • Adenoviruses are being developed for gene and oncolytic therapies.
  • Adenoviral delivery of the tumor suppressor p53 is a key strategy.
  • Understanding resistance mechanisms is crucial for therapeutic development.

Purpose of the Study:

  • To identify genes conferring resistance to adenovirus-delivered p53.
  • To elucidate the mechanism by which resistance occurs.
  • To assess the implications for adenovirus-based cancer therapeutics.

Main Methods:

  • Retroviral suppressor screens were employed.
  • Adenovirus-delivered p53 was used to induce cell death.
  • Expression of tumor antigen LRRC15 was analyzed.
  • Cell surface receptor redistribution was investigated.

Main Results:

  • The tumor antigen LRRC15 was identified as a repressor of cell death induced by adenoviral p53.
  • LRRC15 impedes adenoviral infection by causing coxsackievirus-adenovirus receptor redistribution.
  • LRRC15 reduces adenoviral binding to cell surfaces.
  • LRRC15 does not inhibit p53 function directly.

Conclusions:

  • LRRC15 is a novel repressor of adenoviral p53-mediated cell death.
  • LRRC15 represents a potential resistance mechanism to adenovirus-based therapies.
  • Targeting LRRC15 or its pathway may enhance oncolytic adenovirus efficacy.

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