CD20-targeted measles virus shows high oncolytic specificity in clinical samples from lymphoma patients independent of prior rituximab therapy

Gene Ther. 2011 Mar;18(3):313-7. doi: 10.1038/gt.2010.150. Epub 2010 Nov 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD20 / metabolism
  • Antigens, CD20 / therapeutic use*
  • Flow Cytometry
  • Gene Targeting / methods*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Leukocytes, Mononuclear / pathology
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, B-Cell, Marginal Zone / prevention & control*
  • Measles virus / metabolism*
  • Oncolytic Virotherapy / methods*

Substances

  • Antigens, CD20
  • Green Fluorescent Proteins