Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an $20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intravenous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV.
The Orchidaceae is one of the most famous garden plants, and improvement of the orchid is very important in horticulture field. However, molecular information is largely unknown. We found a Phalaenopsis variety harboring floral organs showing C class homeotic change. Column is composed of the anthers with the receptive stigmatic surface just underneath them in wild type. However the C class variety produced column with sepal or petal like structure at the abaxial side. This is the typical abnormality as C class mutants in plants. Further, wild type looking revertant was found from the meristem tissue cultured population. This result strongly indicates the existence of active transposable element in Phalaenopsis genome. This transposon may enable Phalaenopsis as a good material for molecular genetic analysis in Orchidaceae.
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