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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Published on: January 7, 2019

Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus

Patricia Bach1, Tobias Abel, Christopher Hoffmann

  • 1Medical Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.

Cancer Research
|January 8, 2013
PubMed

Insights

Targeting tumor-initiating cells (TICs) with CD133-retargeted measles viruses (MV) shows promise. These engineered MVs selectively destroy CD133(+) cancer cells, offering a new therapeutic strategy for various cancers.

Area of Science:

  • Oncolytic virotherapy
  • Cancer stem cell targeting

Background:

  • Tumor-initiating cells (TICs) are crucial for cancer development and recurrence.
  • CD133 is a cell surface marker identifying TICs in various cancers, including hepatocellular carcinoma and glioblastoma.
  • Developing targeted therapies against TICs remains a significant challenge in oncology.

Purpose of the Study:

  • To engineer oncolytic measles viruses (MVs) to target CD133+ tumor-initiating cells.
  • To evaluate the efficacy of CD133-targeted MVs in preclinical cancer models.
  • To investigate the mechanisms underlying the enhanced antitumoral activity of targeted MVs.

Main Methods:

  • Retargeting measles virus (MV) to the CD133 cell surface marker, creating MV-141.7 and MV-AC133.
  • In vitro and in vivo testing of MV efficacy in hepatocellular carcinoma, glioma, and colon cancer models.
  • Assessing viral infectivity, tumor cell lysis, and survival rates in NOD/SCID mice.
  • Investigating potential mechanisms for enhanced efficacy, such as receptor overexpression or viral spreading.

Main Results:

  • CD133-targeted MVs (MV-141.7, MV-AC133) selectively infected and lysed CD133(+) tumor cells.
  • Both targeted MVs demonstrated significant antitumoral effects in hepatocellular carcinoma models, outperforming the parental MV-NSe in prolonging survival.
  • Enhanced efficacy was not attributable to target receptor overexpression or increased viral spreading.
  • MV-141.7 also showed efficacy in orthotopic glioma and colon cancer models.

Conclusions:

  • CD133-targeted measles viruses effectively eliminate CD133(+) cells within tumors.
  • These engineered viruses represent a promising tool for cancer research and the development of novel antitumoral strategies.
  • Targeted oncolytic virotherapy offers a selective approach to combat cancer stem cells.

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