5-FC5-Fluorocytosine (antifungal agent)
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Toca 511 & Toca FC is designed to program cancer cells to convert the prodrug 5-FC into the anticancer drug 5-FU, killing tumor cells and leading to activation of the immune system selectively against the tumor via a combination of mechanisms.
Radiation therapy combined with Toca 511 and multiple cycles of 5-FC treatment significantly prolonged survival in pre-established intracranial U87/EGFRvIII radio-resistant glioma models with a median survival of longer than 89 days (median not reached) for the treated group versus 15 days for the control group, supporting the clinical investigation of Toca 511 and 5-FC in combination with radiation in the first-line or recurrent setting for patients with HGG.
In addition, posters were presented at the conference on Toca 511 and 5-FC in combination with temozolomide (TMZ) or radiation in preclinical glioma models, which showed significantly prolonged survival compared to control groups.
5-FC, a commercially available anti-fungal agent, which is administered orally, is converted to 5-FU, an active anti-tumor agent, by the CD enzyme expressed by APS001F in tumors.
Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43.
The FCU1 gene encodes a chimeric enzyme that efficiently converts the non-toxic prodrug 5-FC into the chemotherapeutic drug 5-FU, a well-known drug that has a proven efficacy.