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Retargeted and Stealth-Modified Oncolytic Measles Viruses for Systemic Cancer Therapy in Measles Immune Patients

Eugene S Bah1, Rebecca A Nace2, Kah Whye Peng2

  • 1Medical Scientist Training Program, Mayo Clinic Alix School of Medicine, Rochester, Minnesota.

Molecular Cancer Therapeutics
|August 28, 2020
PubMed

Insights

Engineered measles viruses (MV) resist immune neutralization by swapping surface proteins with canine distemper virus (CDV). This retargeted MV shows promise for cancer therapy in patients immune to measles.

Area of Science:

  • Oncolytic virotherapy
  • Viral engineering
  • Immunology

Background:

  • Measles virus (MV) is limited as an oncolytic agent due to rapid inactivation by neutralizing antibodies.
  • Pre-existing immunity to measles in patients can hinder the efficacy of MV-based therapies.

Purpose of the Study:

  • To engineer a measles virus (MV) that can evade immune neutralization by measles-specific antibodies.
  • To retarget the engineered MV for enhanced cancer cell targeting and therapeutic efficacy in immunocompetent hosts.

Main Methods:

  • Replaced MV surface glycoproteins (H and F) with those from canine distemper virus (CDV).
  • Engineered the CDV H protein to target specific receptors (EGFR or CD38).
  • Assessed viral growth, receptor specificity, neutralization resistance, and in vivo tumor suppression in a mouse model.

Main Results:

  • Recombinant MVs with CDV glycoproteins resisted neutralization by measles-immune human serum.
  • Engineered viruses exhibited specific cell entry, fusion, and target cell killing.
  • An EGFR-retargeted CDV-MV variant demonstrated significant tumor growth inhibition and survival extension in measles-immune mice.

Conclusions:

  • Retargeting MV with engineered CDV glycoproteins creates a "stealth" oncolytic virus.
  • This approach overcomes pre-existing anti-measles immunity, enabling potential systemic cancer therapy in immune patients.

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