Virology, Nebraska Center for
Comparison of Adenoviruses as Oncolytics and Cancer Vaccines in an Immunocompetent B Cell Lymphoma Model
Date of this Version
HUMAN GENE THERAPY 22:1095–1100 (September 2011)
We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in im- munocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing the A20 immunoglobulin ScFv immunogen (Ad-A20) were protected against A20 lymphomas only when the vaccine was delivered before tumor. In contrast, vaccination after tumor initiation failed to increase survival or delay tumor growth. When Ad serotypes from species B, C, D, and E were tested as oncolytics in vitro, A20 cells were most efficiently killed by species D Ads, with intermediate activity by species B Ads. When tested in vivo in immunocompetent BALB/c mice bearing A20 tumors, single intratumoral injection of species D Ad26 and Ad48 were effective at controlling tumor growth. These data demonstrate that in this immunocompetent mouse cancer model, the oncolytic activity of adenoviruses is more potent than their use as a cancer vaccine. These data in immunocompetent mice lend further support to species D Ads as promising oncolytic viruses against B cell cancers.
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Mary Ann Liebert, Inc.