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Toca 521 is a discontinued gene therapy and oncolytic viral vector developed by Tocagen. It utilizes a retroviral replicating vector (RRV) platform to deliver a genetic payload encoding a single-chain variable fragment (scFv) antibody directed against programmed death-ligand 1 (PD-L1). The vector is designed to selectively infect and replicate within actively dividing cancer cells, spreading throughout the tumor mass. Once inside the tumor microenvironment, the infected cells produce and secrete the scFv-PD-L1, which binds to and blocks PD-L1 on both infected and neighboring tumor cells. This localized expression aims to enhance the immune system's ability to recognize and destroy the tumor while minimizing systemic side effects typically associated with monoclonal antibody checkpoint inhibitors. Preclinical studies indicated that this approach could provide superior anti-tumor activity compared to systemic PD-1/PD-L1 inhibition.
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