Talimogene Laherparepvec
Talimogene laherparepvec (formerly called OncoVEX GM-CSF) uses the JS-1 strain of Herpes simplex virus type-1 (HSV-1) with deletions in the ICP34.5 and ICP47 regions. The deletion of the ICP34.5 region enables the virus to selectively replicate in tumour cells [1]. The deletion in the ICP47 region blocks antigen presentation by blocking the activity of the transporter (TAP) responsible for MHC Class I expression in infected cells [2]. Talimogene laherparepvec (T-Vec) also has the GM-CSF gene incorporated into its genome, which allows for the recruitment and stimulation of dendritic cells, enhancing the immune response to tumour cells [3].
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The deletion of ICP47 allows the US11 gene to be under the control of the ICP47 immediate-early promoter instead of the US11 late promoter, enabling earlier viral replication and greater oncolytic potency [1][3]. Phase I clinical trials have been conducted in patients with breast, head and neck, gastrointestinal and skin cancers and phase II and III clinical trials have been conducted in patients with melanoma malignancies[1][4][5]. Phase III clinical trials have demonstrated an increased durable response rate with T-Vec compared to GM-CSF alone [16% to 2%, respectively (p < 0.001)] [5].
Targeted CancerPancreatic
Breast Colorectal Head and Neck Cancers Melanoma |
Phase Isafety of T-VEC in with ipi at full doses showed:
no dose limiting toxicity 1/19 participants had an adverse event [6] |
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