Toca 511 (vocimagene amiretrorepvec) and Toca FC (5-fluorocytosine) are under investigation as a
combination therapy for use in recurrent high-grade gliomas, including GBM. Toca 511 is an
injectable retroviral replicating vector that encodes the prodrug activator enzyme cytosine deaminase
(CD), which is derived from yeast and not found in the human genome. The transfection of the CD
gene into the cancer cell genome by Toca 511 results in the production of the CD enzyme by the
cancer cells. Toca FC, an extended-release version of 5-fluorocytosine (5-FC), is then administered and
converted to 5-fluorouracil (5-FU) at the cancer site by the CD enzyme. 5-FU directly kills cancer cells
and the myeloid-derived suppressor cells (MDSCs) that shield GBM from immune activity, thus
triggering a formerly absent antitumor immune response (Negroni et al., 2007).
Toca 511/FC (vocimagene amiretrorepvec/5-fluorocytosine; Tocagen) is a seemingly effective gene
therapy/small molecule combination in development for recurrent glioblastoma multiforme (GBM)
patients undergoing surgery. The regimen will see limited use in the second-line due to relatively low
tumor resection rates, but could seek out higher utilization in newly diagnosed GBM. Should it present
the necessary Phase III data for approval, the Toca 511/FC combination will be bolstered by the
convenience and lower cost of its mainly oral regimen, as the Toca 511 intratumoral injection is only
required at the initiation of treatment. Furthermore, clinical studies have looked towards the use of
Toca 511/FC in patients ineligible for tumor resection by using either biopsy needle delivery or
convection-enhanced delivery, which would increase the therapy’s target population.
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