Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy

Abstract

With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma. Herein, we review the development of T-VEC, and suggest how it fits into the in the current clinical treatment paradigm, and provide pearls for drug preparation, administration, and monitoring of response to therapy.

From chemotherapy to oncoviruses – modern methods of treatment in metastatic melanoma

“…Wirusy onkolityczne opracowano w celu zapewnienia nowego leku do stosowania w nowotworach złośliwych [35]. Definiuje się je jako wirusy uzyskane metodą inżynierii genetycznej lub występujące naturalnie, które replikują się wyłącznie w komórkach nowotworowych, oszczędzając prawidło-we [36].…”

“…Subsequently, those presenting cells activate a response of T-cells to melanoma cells. Deletion of two insignificant genes, infected cell protein 34.5 (ICP34.5) and ICP47, diminishes viral neuropathogenicity and promotes preferential replication within tumor cells [35][36][37][38][39][40] (Fig. 1).…”

“…W celu oceny oporności nowotworu na odpowiedź immunologiczną wygenerowano limfocyty T CD8+ z ekspresją dwóch Dermatology Review/Przegląd Dermatologiczny 2017/4 Secondly, tumor and viral antigens (such as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)) are exposed after cell lysis to a host immune system, enhancing its tumor-specific response or inducing its anti-tumor activity. This second mechanism is of special interest because it allows for degradation of the neoplastic cells which are not even infected by the virus [35,37]. Talimogene laherparepvec (T-VEC), attenuated herpes simplex virus of type 1 (HSV-1), is engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF) on tumor cells by insertion of the gene encoding human GM-CSF.…”

“…Oncolytic viruses were developed to provide a new management of malignancies [35]. They are defined as genetically engineered or naturally occurring viruses which were designed to replicate only in neoplastic cells, sparing normal ones [36].…”

“…Subjects were randomized and received an intralesional injection of T-VEC (initial dose of 10 6 plaque-forming units (PFU)/ml, followed 3 weeks later by 10 8 PFU/ml and continued every 2 weeks for 12-18 months) or subcutaneous recombinant GM-CSF (125 μg daily for 14 days in a 28-day cycle for 12-18 months) [35,37,40]. More than half (55%) of the patients had not received prior therapy at baseline [37].…”