Species D Adenoviruses as Oncolytics Against B Cell Cancers
Menée in vitro et à l'aide de xénogreffes, cette étude évalue la capacité d'adénovirus de l'espèce D à se répliquer de façon spécifique dans les cellules de cancers à lymphocytes B
Purpose: Oncolytic viruses are self-amplifying anti-cancer 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 since these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine if other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B cell cancers. Experimental Design: 15 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 to 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.