CD20-targeted measles virus shows high oncolytic specificity in clinical samples from lymphoma patients independent of prior rituximab therapy.
New therapeutic modalities for B-cell non-Hodgkin's lymphomas (B-NHL) are needed, especially for relapsing and aggressive subtypes. Toward this end, we previously generated a fully CD20-targeted and armed measles virus, and tested its efficacy in a xenograft model of mantle cell lymphoma (MCL). Here, we quantify its spread in peripheral blood mononuclear cells and/or tissue of patients with different histological subtypes of B-NHL, including splenic marginal zone lymphoma (SMZL). CD20-targeted MV efficiently infects lymphoma cells from SMZL and MCL while sparing most cells in the CD20-negative population, in contrast to the parental vaccine-lineage MV, which infects CD20-positive and CD20-negative cells equally. Rituximab therapy (4-8 months before relapse) did not interfere with the infectivity and specificity of MV(green)H(blind)antiCD20 in patient lymphoma samples. Thus, CD20-targeted oncolytic virotherapy is likely to be effective after previous antiCD20 therapy.
Department of Molecular Medicine, and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Yaiw
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Miest
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Frenzke
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Timm
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Johnston
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Cattaneo
D018951:Antigens, CD20 / Q000378:metabolism / Q000627:therapeutic use*; D005434:Flow Cytometry; D018390:Gene Targeting / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology / Q000517:prevention & control*; D008459:Measles virus / Q000378:metabolism*; D050130:Oncolytic Virotherapy / Q000379:methods*
D018951:Antigens, CD20; D049452:Green Fluorescent Proteins