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Toca 511 & Toca FC
Toca 511 and Toca FC, developed by Tocagen, is a combination treatment currently being investigated in phase I/II trials for recurrent high grade glioma including the notoriously difficult to treat glioblastoma multiforme. Toca 511 (vocimagene amiretrorepvec) is a nonlytic retroviral replicating vector (RRV) that encodes the transgene cytosine deaminase (CD). This enzyme is used to catalyze the conversion of Toca FC, a novel oral extended-release prodrug 5-fluorocytosine (5-FC) to the active 5-fluorouracil (5-FU). Intravenous or intracranial injection of Toca 511 takes place during initial treatment and 3-7 weeks later the patient starts cyclic administration of Toca FC.1,2,3 The phase I/II trials in humans have shown similar results of patients exceeding the average life expectancy of high grade gliomas.4
== Mechanism of action ==
Retroviruses, once inside the target cell, use reverse transcriptase to produce DNA from the RNA present in the virus. Toca 511 is based on the gamma retrovirus, murine leukemia (MLV).5 The virus has many innate properties that are suitable for targeted cancer treatment. One of the most important properties is the reproduction mechanism that occurs without cytolysis of the host cell. In non-lytic reproduction, the infected cell continuously forms small buds that are pinched off containing the virus to allow rapid infection. Another property is the requirement for cell division. Infection is limited to mitotically active cells. These two properties present an ideal candidate vector for modification. The lack of cytolysis in the host cell prevents an immune response and the necessity for the cell to be dividing allows localization to cancerous tumors. As an oncolytic agent, the mechanism uses the rapid mitotic activity of the cancerous tumor cells to spread the therapeutic gene in an effective and controlled manner.5 In Toca 511, the insertion of the CD transgene into the active tumor catalyzes the treatment. The expression of CD by the tumor allows intratumoral conversion of 5-FC to 5-FU.6 This allows the cytotoxic 5-FU to be maintained within the tumor cell. A second mechanism of action is proposed based upon recent data. Post-treatment, a systemic anticancer immune response is present that selectively acts against the cancerous cells.4,7
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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