Details

Autor(en) / Beteiligte

• Wechman, Stephen L.
• Rao, Xiao-Mei
• McMasters, Kelly Marc
• Zhou, Heshan Sam

Titel

Abstract 3753: Improved oncolytic virotherapy by increasing adenovirus spread

Ist Teil von

• Cancer research (Chicago, Ill.), 2016-07, Vol.76 (14_Supplement), p.3753-3753

Erscheinungsjahr

2016

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract Lung cancer is the leading cause of cancer-related death worldwide and kills more patients than the next four cancers combined (Colon, breast, prostate, and pancreas). Currently available lung cancer treatments have not been effective. Therefore the development of novel lung cancer therapeutics is of critical importance. One emerging treatment option is the use of E1b-deleted adenoviruses (Ads) which preferentially lyse cancer cells. Although E1b-deleted Ads have been applied in clinical trials, their efficacy remains low. We have developed a novel oncolytic vector, AdUV, via the bioselection of the cancer selective E1b-deleted Ad Adhz60. We have demonstrated that AdUV is much more potent against multiple cancer cell lines than the parental vector Adhz60 in vitro and suppressed tumor growth in vivo. We compared AdUV treated cells to cells treated with the wildtype Ad5 and the E1b-deleted Adhz60. AdUV lysed A549 lung cancer cells more efficiently than Adhz60, but neither AdUV nor Adhz60 killed MRC5 and HBEC normal lung cells. Possible mechanisms of action were then investigated to determine how AdUV lysed A549 cells more effectively. AdUV virions were shown to release from infected A549 cells and induce autophagy more effectively than both Adhz60 and Ad5. Autophagy induction is known to support Ad replication and spread through cancer cell monolayers. The plaque assay was used to verify if AdUV could spread more effectively than Ad5 and Adhz60 because viruses which efficiently replicate and release from cells are known to form larger plaques. The average size of plaques formed by AdUV is 340% and 214% larger than those plaques formed by Adhz60 and Ad5, respectively. In vivo, AdUV was non-lethal to athymic nude mice and strongly suppressed A549-xenograft tumor growth, prolonging murine survival. These results indicate that AdUV is a more effective, safe oncolytic Ad vector. Our findings also demonstrate the utility of bioselection of the generation of more effective cancer therapeutic vectors. Citation Format: Stephen L. Wechman, Xiao-Mei Rao, Kelly Marc McMasters, Heshan Sam Zhou. Improved oncolytic virotherapy by increasing adenovirus spread. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3753.