Talimogene laherparepvec (Imlygic)

概览

Talimogene laherparepvec is a genetically modified virus used to treat recurrent melanoma, or metastatic melanoma.

作用机制

Talimogene laherparepvec is an oncolytic immunotherapy that is derived from Herpes Simplex Virus type-1 (HSV-1) . It has been modified to replicate within tumor cells and to produce the immune response stimulatory protein, human GM-CSF (granulocyte macrophage colony stimulating factor) . The medication causes the death of tumor cells and the release of tumor-derived antigens . It is believed that together with GM-CSF, talimogene laherparepvec can promote a systemic anti-tumor immune response and an effector T-cell response . Mice subjects involved in talimogene laherparepvec treatment studies that had complete regression of their primary tumors following therapy were resistant to subsequent tumor rechallenge . The genetic modifications to talimogene laherparepvec from HSV-1 include deletion of the ICP34.5 and ICP47 genes . Whereas anti-viral immune responses defend normal cells following infection by talimogene laherparepvec, tumors have been shown to be susceptible to injury and cell death from ICP34.5-deficient HSV-1 derived viruses, including talimogene laherparepvec . Moreover, deletion of ICP47 prevents the down-regulation of antigen presentation molecules in the targeted tumor cells and increases the expression of the HSV US11 gene, thereby enhancing the talimogene laherparepvec viral replication in tumor cells and increases chances of tumor cell injury and death . Although the talimogene laherparepvec virus is specifically modified to infect and multiply inside melanoma cells and uses melanoma cells' own machinery to multiply, the medication is not designed to multiply inside healthy cells, which it is also capable of entering .

适应症

This medication is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable, cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery . Elsewhere, the EMA notes that the agent is indicated for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral diseases .

• Unresectable Skin Lesion