Preliminary evaluation of safety of conditionally replication adenovirus M4
- 47 Downloads
Conditionally replication adenovirus M4, which was constructed in our lab, was proved to have good clinical application prospect for its good anti-tumor and anti-metastasis effect. However, clinically applying M4 faces many problems. One of the most important is the safety of M4. In this study, we investigated the safety of M4 by comparing with Adv-TK, which was proved to be safe in I–III phase clinical trials. M4 and Adv-TK were injected into mice via the tail vein separately, and the mice were sacrificed at the indicated time. Blood was collected for biochemical tests, the liver was harvested for hematoxylin and eosin (H&E) staining and viral quantification, and splenic lymphocytes were separated for adenovirus specific cellular immune response. Our results showed that M4 had no obvious effect on mouse general symptoms. A transient reversible infiltration of inflammatory cells in collect abbacy was only observed in M4 group, and a transient slight increase in Cr level was detected both after M4 and Adv-TK injection. The adenovirus specific cellular immune response induced by M4 was similar to that by Adv-TK, and the distribution and metabolism of M4 in the mouse liver were also similar to those of Adv-TK. It was concluded that conditionally replication adenovirus M4 had the same safety as Adv-TK. The study provides safety basis for the coming clinical trials of M4.
Key wordsconditionally replication adenovirus M4 safety blood biochemistry distribution
Unable to display preview. Download preview PDF.
- 2.Emunaitis J, Ganly I, Khuri F, et al. Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res, 2000,60(22):6359–6366Google Scholar
- 4.Freytag SO, Stricker H, Pegg J, et al. Phase I study of replication-competent adenovirus-mediated double- suicide gene therapy in combination with conventional- dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer. Cancer Res, 2003,63(21):7497–7506PubMedGoogle Scholar
- 5.Page JG, Tian B, Schweikart K, et al. Identifying the safety profile of a novel infectivity-enhanced conditionally replicative adenovirus, Ad5-delta24-RGD, in anticipation of a phase I trial for recurrent ovarian cancer. Am J Obstet Gynecol, 2007,196(4):389 e1–9; discussion 389 e9–10PubMedCrossRefGoogle Scholar