期刊
EXPERT OPINION ON BIOLOGICAL THERAPY
卷 21, 期 9, 页码 1199-1214出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14712598.2021.1902982
关键词
Retroviral vector; cancer; gene therapy; immunotherapy
资金
- Alliance for Cancer Gene Therapy (ACGT)
- National Cancer Institute (NCI) [R01 CA213119]
- National Institute of Neurological Disorders and Stroke (NINDS) [R21 NS104454, R25 NS108937]
- Department of Defense Congressionally Directed Medical Research Programs (CDMRP) [W81XWH-19-1-0349/CA181015P1]
Toca 511 has shown promising results in early-stage clinical trials, progressing to a Phase III trial, however, the results announced in late 2019 were overall negative. Further clinical investigation and development of RRV with other transgene payloads is warranted.
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.
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