Toca 511 (vocimagene amiretrorepvec), a non-lytic, amphotropic retroviral replicating vector (RRV), encodes and delivers a functionally optimized yeast cytosine deaminase (CD) gene to tumors. In orthotopic glioma models treated with Toca 511 and 5-fluorocytosine (5-FC) the CD enzyme within infected cells converts 5-FC to 5-fluorouracil (5-FU), resulting in tumor killing. Toca 511, delivered locally either by intratumoral injection or injection into the resection bed, in combination with subsequent oral extended-release 5-FC (Toca FC), is under clinical investigation in patients with recurrent high-grade glioma (HGG). If feasible, intravenous (IV) administration of vectors is less invasive, can easily be repeated if desirable, and may be applicable to other tumor types. Here, we present preclinical data that supported development of an IV administration protocol. First we show that IV administration of Toca 511 in a pre-clinical model did not lead to widespread or uncontrolled replication of the RVV. No, or low, viral DNA was found in the blood and most of the tissues examined 180 days after Toca 511 administration. We also show that RRV administered IV leads to efficient infection and spread of the vector containing GFP gene (Toca GFP) through tumors in both immune-competent and immune-compromised animal models. However initial vector localization within the tumor appeared dependent on the mode of administration. Long-term survival was observed in immune-competent mice when Toca 511 was administered IV or intracranially (IC) in combination with 5-FC treatment, and this combination was well tolerated in the pre-clinical models. Enhanced survival could also be achieved in animals with preexisting immune response to vector supporting the potential for repeated administration. Based on these and other supporting data, a clinical trial investigating IV administration of Toca 511 in patients with recurrent HGG is currently open and enrolling.
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2024.
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#12
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Altmetric has tracked 34,054,827 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,493 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.9. This one has done well, scoring higher than 79% of its peers.
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