Abstract
Talimogene laherparepvec (T-VEC) is a modified oncolytic herpes Simplex virus, type 1 (HSV-1) encoding granulocyte-macrophage colony stimulating factor (GM-CSF). T-VEC is adapted for selective replication in melanoma cells and GM-CSF was expressed to augment host anti-tumor immunity. T-VEC is indicated for the local treatment of melanoma recurrent after primary surgery and is the first-in-class oncolytic virus to achieve approval by the FDA in 2015. This review will describe the progress made in advancing T-VEC to the most appropriate melanoma patients, expansion to patients with non-melanoma cancers and clinical trial results of T-VEC combination studies. Further, strategies to identify predictive biomarkers of therapeutic response to T-VEC will be discussed. Finally, a brief outline of high-priority future directions for investigation of T-VEC and other promising oncolytic viruses will set the stage for a best-in-class oncolytic virus to bring the maximum benefit of this emerging class of anti-cancer agents to patients with cancer.
Highlights
Oncolytic viruses (OV) are a new class of anti-cancer therapeutic agents that utilize native or genetically modified viruses to treat cancer
In the OPTiM trial, 54% of patients exhibited some degree of disease progression based on caliper measurement or imaging prior to achieving an objective response, suggesting that pseudoprogression may be possible with Talimogene laherparepvec (T-VEC) treatment. Based on these data T-VEC was approved by the U.S FDA in 2015 for the local treatment of melanoma that recurs after initial surgery and T-VEC was approved in Europe in 2016 for the local treatment of melanoma patients with stage IIIB-IVM1a disease
In our lab we found that loss of STING expression, a known biomarker for anti-programmed cell death 1 (PD-1) resistance, was associated with improved oncolytic activity of T-VEC in vitro (Bommareddy et al, 2019)
Summary
Oncolytic viruses (OV) are a new class of anti-cancer therapeutic agents that utilize native or genetically modified viruses to treat cancer. While early reports of tumor regression in patients infected with various viruses has been reports for over a century, advances in molecular genetics and virology have only recently allowed a more directed approach to therapeutic development in this area (Kucerova and Cervinkova, 2016). Based on these early observations, it was thought that OVs most likely mediated tumor regression by preferentially infected and killing tumor cells. We will mention some recent insights into biomarkers of OV responses and complete the review by discussing anticipated future directions for T-VEC and other OVs in clinical development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
