Oncolytic adenovirus based on serotype 3 - PubMed (original) (raw)
doi: 10.1038/cgt.2010.79. Epub 2010 Dec 24.
G Bauerschmitz, S Hemmi, S Lavilla-Alonso, I Diaconu, K Guse, A Koski, R A Desmond, M Lappalainen, A Kanerva, V Cerullo, S Pesonen, A Hemminki
Affiliations
- PMID: 21183947
- DOI: 10.1038/cgt.2010.79
Free article
Oncolytic adenovirus based on serotype 3
O Hemminki et al. Cancer Gene Ther. 2011 Apr.
Free article
Abstract
Oncolytic adenoviruses have been safe in clinical trials but the efficacy has been mostly limited. All published trials have been performed with serotype 5 based viruses. The expression level of the Ad5 receptor CAR may be variable in advanced tumors. In contrast, the Ad3 receptor remains unclear, but is known to be abundantly expressed in most tumors. Therefore, we hypothesized that a fully serotype 3 oncolytic adenovirus might be useful for treating cancer. Patients exposed to adenoviruses develop high titers of serotype-specific neutralizing antibodies, which might compromise re-administration. Thus, having different serotype oncolytic viruses available might facilitate repeated dosing in humans. Ad3-hTERT-E1A is a fully serotype 3 oncolytic adenovirus controlled by the promoter of the catalytic domain of human telomerase. It was effective in vitro on cell lines representing seven major cancer types, although low toxicity was seen in non-malignant cells. In vivo, the virus had anti-tumor efficacy in three different animal models. Although in vitro oncolysis mediated by Ad3-hTERT-E1A and wild-type Ad3 occurred more slowly than with Ad5 or Ad5/3 (Ad3 fiber knob in Ad5) based viruses, in vivo the virus was at least as potent as controls. Anti-tumor efficacy was retained in presence of neutralizing anti-Ad5 antibodies whereas Ad5 based controls were blocked. In summary, we report generation of a non-Ad5 based oncolytic adenovirus, which might be useful for testing in cancer patients, especially in the context of high anti-Ad5 neutralizing antibodies.
Similar articles
- Retargeting improves the efficacy of a telomerase-dependent oncolytic adenovirus for head and neck cancer.
Toivonen R, Suominen E, Grenman R, Savontaus M. Toivonen R, et al. Oncol Rep. 2009 Jan;21(1):165-71. Oncol Rep. 2009. PMID: 19082458 - A capsid-modified, conditionally replicating oncolytic adenovirus vector expressing TRAIL Leads to enhanced cancer cell killing in human glioblastoma models.
Wohlfahrt ME, Beard BC, Lieber A, Kiem HP. Wohlfahrt ME, et al. Cancer Res. 2007 Sep 15;67(18):8783-90. doi: 10.1158/0008-5472.CAN-07-0357. Cancer Res. 2007. PMID: 17875719 - Improved glioblastoma treatment with Ad5/35 fiber chimeric conditionally replicating adenoviruses.
Hoffmann D, Meyer B, Wildner O. Hoffmann D, et al. J Gene Med. 2007 Sep;9(9):764-78. doi: 10.1002/jgm.1076. J Gene Med. 2007. PMID: 17640083 - Telomerase-specific oncolytic virotherapy for human gastrointestinal cancer.
Fujiwara T, Shirakawa Y, Kagawa S. Fujiwara T, et al. Expert Rev Anticancer Ther. 2011 Apr;11(4):525-32. doi: 10.1586/era.10.200. Expert Rev Anticancer Ther. 2011. PMID: 21504319 Review. - [Theranostic application of telomerase-specific oncolytic adenovirus for human cancer].
Fujiwara T, Tanaka N. Fujiwara T, et al. Nihon Rinsho. 2007 Oct;65(10):1913-22. Nihon Rinsho. 2007. PMID: 17926546 Review. Japanese.
Cited by
- Strategies for engineering oncolytic viruses to enhance cancer immunotherapy.
Yin ZS, Wang Z. Yin ZS, et al. Front Pharmacol. 2024 Sep 6;15:1450203. doi: 10.3389/fphar.2024.1450203. eCollection 2024. Front Pharmacol. 2024. PMID: 39309012 Free PMC article. Review. - Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.
Gujar S, Pol JG, Kumar V, Lizarralde-Guerrero M, Konda P, Kroemer G, Bell JC. Gujar S, et al. Nat Protoc. 2024 Sep;19(9):2540-2570. doi: 10.1038/s41596-024-00985-1. Epub 2024 May 20. Nat Protoc. 2024. PMID: 38769145 Review. - Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus.
Ono R, Nishimae F, Wakida T, Sakurai F, Mizuguchi H. Ono R, et al. Sci Rep. 2022 Dec 13;12(1):21560. doi: 10.1038/s41598-022-26030-3. Sci Rep. 2022. PMID: 36513733 Free PMC article. - Adenovirus-Inspired Virus-Like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses.
Besson S, Laurin D, Chauvière C, Thépaut M, Kleman JP, Pezet M, Manches O, Fieschi F, Aspord C, Fender P. Besson S, et al. Biomedicines. 2022 Nov 10;10(11):2881. doi: 10.3390/biomedicines10112881. Biomedicines. 2022. PMID: 36359404 Free PMC article. - Nonhuman Primate Adenoviruses of the Human Adenovirus B Species Are Potent and Broadly Acting Oncolytic Vector Candidates.
Bots STF, Kemp V, Cramer SJ, van den Wollenberg DJM, Hornsveld M, Lamfers MLM, van der Pluijm G, Hoeben RC. Bots STF, et al. Hum Gene Ther. 2022 Mar;33(5-6):275-289. doi: 10.1089/hum.2021.216. Hum Gene Ther. 2022. PMID: 34861769 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources