Measles Virus entry through the signaling lymphocyte activation molecule governs efficacy of mantle cell lymphoma radiovirotherapy

Tanner S. Miest, Marie Frenzke, Roberto Cattaneo

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We developed here a vaccine-identical measles virus (MV) as an oncolytic agent against mantle cell lymphoma (MCL), an aggressive B-cell non-Hodgkin's lymphoma that is difficult to cure but radiosensitive. We armed the virus with the sodium-iodide symporter, which concentrates iodide within infected cells enabling noninvasive imaging and combination radiovirotherapy. Through high-resolution in vivo and ex vivo imaging, we visualized the spread of infections in primary and metastatic tumors for over 2 weeks after therapy, documenting homogeneous virus seeding and spread restricted to perfused tissue. Infection of metastases was more rapid and intense than primary tumors, achieving isotope uptake within about threefold the efficiency of the thyroid. Virotherapy combined with systemic 131 I resulted in more rapid disease regression than either therapy alone. In addition to ubiquitous CD46, vaccine MV retains cell entry through its immune cell-specific receptor signaling lymphocytic activation molecule (SLAM). We asked whether both receptors could sustain effective oncolysis of MCL. Strikingly, only SLAM-dependent entry sustained efficient viral spread, tumor regression, and prolonged survival. These observations shift the focus of future clinical trials to SLAM-expressing hematologic malignancies and suggest that oncolytic vectors may depend on tissue-specific receptors for both cell entry and activation of responses assisting their replication.

Original languageEnglish (US)
Pages (from-to)2019-2031
Number of pages13
JournalMolecular Therapy
Volume21
Issue number11
DOIs
StatePublished - Nov 2013

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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