Novel Oncolytic Vaccinia Virus

· TGI - Cancer, TGI - Omics Medicine
Authors

Oncolytic viral therapies have shown such promise in preclinical trials as a novel cancer treatment modality, that several phase I and II trials are already underway [1]. Oncolytic vaccinia virus strains have been of particular interest due to several advantages. Vaccinia’s large 192-kb genome [2]enables a large amount of foreign DNA to be incorporated without significantly reducing the replication efficiency of the virus, which has been shown to be the case with some adenoviruses [3]. It has fast and efficient replication, and cytoplasmic replication of the virus lessens the chance of recombination or integration of viral DNA into cells [3][4]. Vaccinia has also been shown capable of immune evasion and of infecting a wide variety of cells [4][5][6][7][8][9][10][11][12]13. Perhaps most importantly, its safety profile after its use as a live vaccine in the WHO’s smallpox vaccination makes it particularly attractive as an oncolytic agent and gene vector [14]. Furthering its safety profile, vaccinia immunoglobulin and antiviral drugs are available if needed [15].

Previously they reported on the construction and generation of a novel attenuated replication-competent vaccinia virus (VACV), GLV-1h153, a derivative of parental virus GLV-1h68 engineered to carry the human sodium iodide symporter (hNIS) [16]. hNIS, an intrinsic plasma membrane protein, facilitates transport of several carrier-free radiotracers such as radioiodine and technecium-pertechnetate (99mTcO4[17]. GLV-1h153 facilitated enhanced dose-dependent radiouptake in cell culture and effective replication and killing of pancreatic cancer cells both in cell culture and in animal models, without hindering replication or oncolytic capability. Furthermore, GLV-1h153 facilitated enhanced radiouptake in tumors which was readily detected by positron emission tomography (PET), a deep tissue imaging modality.

The noninvasive tracking of virus delivery may offer clinicians the ability to correlate efficacy and therapy, monitor potential viral toxicity, and provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases [18][19].

This study aimed to further this work by determining the tissue distribution and spread of GLV-1h153, and explore the timing dynamics between viral infection, uptake of radioiodine, and oncolysis. The optical, histologic, and deep tissue viral detection capability was investigated. Moreover, the radioiodine retention capacity of tumors transduced with hNIS via GLV-1h153 determined and whether PET imaging can be accurately quantitative. Finally, the potential to detect virus replication in tumors treated systemically via both 124I-PET and 99mTcO4-mediated gamma-scintigraphy was investigated.

source

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041647

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