Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

Elena V. Shashkova; Shannon M. May; Michael A. Barry

doi:10.1016/j.virol.2009.08.038

Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

Elena V. Shashkova, Shannon M. May, Michael A. Barry

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.

Original language	English (US)
Pages (from-to)	311-320
Number of pages	10
Journal	Virology
Volume	394
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2009.08.038
State	Published - Nov 25 2009

Keywords

Adenovirus
Kupffer cells
Oncolytic viruses
Toxicity
Xenograft model antitumor assays

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2009.08.038

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title = "Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents",

abstract = "Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.",

keywords = "Adenovirus, Kupffer cells, Oncolytic viruses, Toxicity, Xenograft model antitumor assays",

author = "Shashkova, {Elena V.} and May, {Shannon M.} and Barry, {Michael A.}",

note = "Funding Information: We thank Konstantin Doronin for valuable suggestions and Roberto Cattaneo for CD46 transgenic mice. We thank Mary Barry and DeAnn Frederixon for helpful technical assistance. This work was supported by the NIH P50 CA91956 Prostate Cancer SPORE grant to Mayo Clinic.",

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doi = "10.1016/j.virol.2009.08.038",

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AU - Barry, Michael A.

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PY - 2009/11/25

Y1 - 2009/11/25

N2 - Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.

AB - Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.

KW - Adenovirus

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KW - Oncolytic viruses

KW - Toxicity

KW - Xenograft model antitumor assays

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Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

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