Species D adenoviruses as oncolytics against B-cell cancers

Christopher Y. Chen, Julien S. Senac, Eric A Weaver, Shannon M. May, Diane F. Jelinek, Philip Greipp, Thomas Witzig, Michael A. Barry

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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 speciesDadenoviruses 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.

Original languageEnglish (US)
Pages (from-to)6712-6722
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number21
DOIs
StatePublished - Nov 1 2011

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Adenoviridae
B-Lymphocytes
Viruses
Neoplasms
Heterografts
Lymphoma
Oncolytic Viruses
Cell Line
Antineoplastic Agents
Research Design
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chen, C. Y., Senac, J. S., Weaver, E. A., May, S. M., Jelinek, D. F., Greipp, P., ... Barry, M. A. (2011). Species D adenoviruses as oncolytics against B-cell cancers. Clinical Cancer Research, 17(21), 6712-6722. https://doi.org/10.1158/1078-0432.CCR-11-0968

Species D adenoviruses as oncolytics against B-cell cancers. / Chen, Christopher Y.; Senac, Julien S.; Weaver, Eric A; May, Shannon M.; Jelinek, Diane F.; Greipp, Philip; Witzig, Thomas; Barry, Michael A.

In: Clinical Cancer Research, Vol. 17, No. 21, 01.11.2011, p. 6712-6722.

Research output: Contribution to journalArticle

Chen, CY, Senac, JS, Weaver, EA, May, SM, Jelinek, DF, Greipp, P, Witzig, T & Barry, MA 2011, 'Species D adenoviruses as oncolytics against B-cell cancers', Clinical Cancer Research, vol. 17, no. 21, pp. 6712-6722. https://doi.org/10.1158/1078-0432.CCR-11-0968
Chen, Christopher Y. ; Senac, Julien S. ; Weaver, Eric A ; May, Shannon M. ; Jelinek, Diane F. ; Greipp, Philip ; Witzig, Thomas ; Barry, Michael A. / Species D adenoviruses as oncolytics against B-cell cancers. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 21. pp. 6712-6722.
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