Clinical development of retroviral replicating vector Toca 511 for gene therapy of cancer
Sara Collins, Ashish H. Shah, Derek Ostertag, Noriyuki Kasahara, Douglas J. Jolly
Abstract
INTRODUCTION: The use of tumor-selectively replicating viruses is a rapidly expanding field that is showing considerable promise for cancer treatment. Retroviral replicating vectors (RRV) are unique among the various replication-competent viruses currently being investigated for potential clinical utility, because they permanently integrate into the cancer cell genome and are capable of long-term persistence within tumors. RRV can mediate efficient tumor-specific delivery of prodrug activator genes, and subsequent prodrug treatment leads to synchronized cell killing of infected cancer cells, as well as activation of antitumor immune responses. AREAS COVERED: Here we review preclinical studies supporting bench-to-bedside translation of Toca 511, an optimized RRV for prodrug activator gene therapy, the results from Phase I through III clinical trials to date, and potential future directions for this therapy as well as other clinical candidate RRV. EXPERT OPINION: Toca 511 has shown highly promising results in early-stage clinical trials. This vector progressed to a registrational Phase III trial, but the results announced in late 2019 appeared negative overall. However, the median prodrug dosing schedule was not optimal, and promising possible efficacy was observed in some prespecified subgroups. Further clinical investigation, as well as development of RRV with other transgene payloads, is merited.