Replicating poxviruses for human cancer therapy

Abstract

Naturally occurring oncolytic viruses are live, replication-proficient viruses that specifically infect human cancer cells while sparing normal cell counterparts. Since the eradication of smallpox in the 1970s with the aid of vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown various degrees of safety and efficacy in pre-clinical or clinical application for human anti-cancer therapeutics. Furthermore, we have recently discovered that cellular tumor suppressor genes are important in determining poxviral oncolytic tropism. Since carcinogenesis is a multi-step process involving accumulation of both oncogene and tumor suppressor gene abnormalities, it is interesting that poxvirus can exploit abnormal cellular tumor suppressor signaling for its oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ATM, and RB are known to play important roles in genomic fidelity/maintenance. Thus, tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to accumulation of genetic defects, which would in turn result in oncolytic virus susceptibility. This review outlines the characteristics of oncolytic poxvirus strains, including vaccinia, myxoma, and squirrelpox virus, recent progress in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and poxviral oncolytic tropism, and the associated preclinical/clinical implications. I would also like to propose future directions in the utility of poxviruses for oncolytic virotherapy.

Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines

“…Oncolytic vaccinia viruses (VVs) have been shown to successfully and specifically infect tumor cells and lyse them. 22,23 However, VVs "armed" with cytokines or chemokines have been shown to be even more effective by inducing anti-tumor immune responses. [24][25][26][27] As an example, we reported enhanced anti-tumor efficacy with a VV expressing b.…”

Advance on research of oncolytic vaccinia virus inhibits tumor cells

“…F1L 缺 失 ; 插 入EGFP [27] Copenhagen株 VV-FCU1 TK缺失, 插入融合自杀基因FCU1 [28] Tian Tan 株 VG9-GMCSF TK缺失, 插入GM-CSF基因 [29] Modified Vaccinia virus ANKARA MVA-5T4 插入human oncofetal antigen 5T4基因 [30,31] LC16M 系 列 MRVV miRNA let-7a调节的靶向B5R的3′非翻译区 [30,32] 染等压力条件下, 往往会产生诸如热休克蛋白(heat shock proteins, HSPs)之类的压力反应蛋白 [18] . Jindal 和Young [43] 曾报道痘苗病毒感染后能够引起HSP90 和HSP60 mRNA含量的少量增加, 以及HSP70 mRNA 水平的大幅度增长.…”

Target Therapy With Vaccinia Virus Harboring IL-24 For Human Breast Cancer

“…Oncolytic vaccinia virus represents a potential strategy for cancer therapy due to its appealing features such as extensive safety as a live vaccine and efficient delivery to metastatic tumors [2][3][4]. Besides, oncolytic vaccinia virus can also be used as gene Ivyspring International Publisher expression carrier due to its large size and expression using its own enzyme systems.…”