Our Breakthrough CAGT Technology

Toca 511, also known as vocimagene amiretrorepvec [pronounced voe sim a jeen am i re troe rep vek], is the key novel component of Tocagen’s first Product Candidate, Toca 511 & Toca FC. Toca 511 was developed using our breakthrough Controlled Active Gene Transfer (CAGT) technology. The CAGT platform is a Retroviral Replicating Vector (RRV) that carries the complete complement of viral genes (gag, pol, env) which allow viral replication and subsequent delivery of a therapeutic gene throughout a tumor. RRV’s replicate by budding from the host cell, leaving the host cell intact. This budding mechanism allows cancer cells to become “factories” for generating RRV particles, which can then spread through the tumor. With this unique budding mechanism, a single dose of RRV (e.g. Toca 511) may be sufficient to achieve persistent gene therapy throughout the tumor.

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Electron micrographs used with permission from: Retroviruses. JM Coffin, SH Hughes, and HE Varmus. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997. Page 30. Copyright © 1997, Cold Spring Harbor Laboratory Press.

The CAGT technology allows the RRV’s to hide and spread in cancer cells because cancer cells typically have genetic mutations resulting in defects in innate and acquired immunity. RRV’s are controlled by the immune system in healthy cells resulting in selective infection of the cancer cells.

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Data from in vivo pre-clinical animal studies demonstrate efficient gene delivery throughout a tumor within approximately 3 weeks, as shown below:

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In contrast, non-replicating viruses cannot spread and oncolytic viruses often cause an inflammatory response that does not allow the oncolytic virus to “hide” from the immune system. The unique combination of features of CAGT vectors may address these key challenges because they are designed to persistently infect cancer cells resulting in infection throughout a tumor.