title: Measles virus entry through the signaling lymphocyte activation molecule governs efficacy of mantle cell lymphoma radiovirotherapy.
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.
authors.affiliation: 1] Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA [2] Virology and Gene Therapy Track, Mayo Graduate School, Rochester, Minnesota, USA.
authors.forename: Tanner S
authors.initials: TS
authors.lastname: Miest
authors.forename: Marie
authors.initials: M
authors.lastname: Frenzke
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D003412:Cricetulus; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D020522:Lymphoma, Mantle-Cell / Q000532:radiotherapy / Q000628:therapy* / Q000821:virology; D008458:Measles Vaccine; D008459:Measles virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D050130:Oncolytic Virotherapy / Q000379:methods*; D011878:Radiotherapy / Q000379:methods; D011956:Receptors, Cell Surface / Q000276:immunology*; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014709:Vero Cells; D053586:Virus Internalization; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D015703:Antigens, CD; D007457:Iodine Radioisotopes; D008458:Measles Vaccine; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D027981:Symporters; D000099209:Sodium-Iodide Symporters
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