title: Species D adenoviruses as oncolytics against B-cell cancers.
abstract: OBJECTIVE
  Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.
  
  
  METHODS
  Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers for their ability to infect, replicate in, and kill these cells. Select viruses were also tested against B-cell cancer xenografts in immunodeficient mice.
  
  
  RESULTS
  Species D adenoviruses mediated most robust killing against a range of B-cell cancer cell lines, against primary patient marginal zone lymphoma cells, and against primary patient CD138+ myeloma cells in vitro. When injected into xenografts in vivo, single treatment with select species D viruses Ad26 and Ad45 delayed lymphoma growth.
  
  
  CONCLUSIONS
  Relatively unstudied species D adenoviruses have a unique ability to infect and replicate in B-cell cancers as compared with other adenovirus species. These data suggest these viruses have unique biology in B cells and support translation of novel species D adenoviruses as oncolytics against B-cell cancers.
authors: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55902, USA.
authors: Christopher Y
authors: CY
authors: Chen
authors: Julien S
authors: JS
authors: Senac
authors: Eric A
authors: EA
authors: Weaver
authors: Shannon M
authors: SM
authors: May
authors: Diane F
authors: DF
authors: Jelinek
authors: Philip
authors: P
authors: Greipp
authors: Thomas
authors: T
authors: Witzig
authors: Michael A
authors: MA
authors: Barry
mesh_terms: D000258:Adenovirus Infections, Human / Q000821:virology; D000260:Adenoviruses, Human / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy* / Q000821:virology; D016393:Lymphoma, B-Cell / Q000628:therapy* / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology*; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays