Oncolytic tanapoxvirus expressing FliC causes regression of human colorectal cancer xenografts in nude mice
نویسندگان
چکیده
Colorectal cancers are significant causes of morbidity and mortality and existing therapies often perform poorly for individuals afflicted with advanced disease. Oncolytic virotherapy is an emerging therapeutic modality with great promise for addressing this medical need. Herein we describe the in vivo testing of recombinant variants of the tanapoxvirus (TPV). Recombinant viruses were made ablated for either the 66R gene (encoding a thymidine kinase), the 2L gene (encoding a TNF-binding protein), or both. Some of the recombinants were armed to express mouse chemotactic protein 1 (mCCL2/mMCP-1), mouse granulocyte-monocyte colony stimulating factor (mGM-CSF), or bacterial flagellin (FliC). Tumors were induced in athymic nude mice by implantation of HCT 116 cells and subsequently treated by a single intratumoral injection of one of the recombinant TPVs. Histological examination showed a common neoplastic cell type and a range of immune cell infiltration, necrosis, and tumor cell organization. Significant regression was seen in tumors treated with virus TPV/Δ2L/Δ66R/fliC, and to a lesser extent the recombinants TPV/Δ2L and TPV/Δ66R. Our results suggest that oncolytic recombinants of the TPV armed with activators of the innate immune response may be effective virotherapeutic agents for colorectal cancers in humans and should be explored further to fully realize their potential.
منابع مشابه
Synthesis and Application of New Gadolinium-Porphyrins as Potential MR Imaging Contrast Agents for Cancer Detection in Nude Mice
Two new potential magnetic resonance imaging contrast agents, Gd-hematoporphyrin (Gd-H) and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd TCP), were synthesized and applied to nude mice with human melanoma (MM 138) xenografts. These agents showed a high relaxivity because of their greater potential to coordinate water molecules. The reduction of T1 relaxation times of 16 and 21% was observed i...
متن کاملInjectable Estradiol Valerate, as a Substitute for Estradiol Pellets in Breast Cancer Animal Model
The ability to maintain and study human tissues in in-vivo environment has proved to be a valuable tool in breast cancer research for several decades. The most widely tissues have been xenografts established human breast cancer cell lines into athymic nude mice. The aim of this study was to provide a new accurate and affordable method for the establishment of breast cancer xenograftin nude mice...
متن کاملNatural Oncolytic Activity of Live-Attenuated Measles Virus against Human Lung and Colorectal Adenocarcinomas
Lung and colorectal cancers are responsible for approximately 2 million deaths each year worldwide. Despite continual improvements, clinical management of these diseases remains challenging and development of novel therapies with increased efficacy is critical to address these major public health issues. Oncolytic viruses have shown promising results against cancers that are resistant to conven...
متن کاملApoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression
A recombinant vaccinia virus VVdGF-ApoS24/2 expressing apoptin selectively kills human cancer cells in vitro [Kochneva et al., 2013]. We compared the oncolytic activity of this recombinant with that of the parental strain L-IVP using a model of human A431 carcinoma xenografts in nude mice. Single intratumoral injections (2×10^7 PFU/mouse) of the viruses produced a dramatic decrease in tumor vol...
متن کاملCD133-targeted oncolytic adenovirus demonstrates anti-tumor effect in colorectal cancer
Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examin...
متن کامل