Wednesday, March 20, 2013

Melanoma and TVEC

Amgen announced success with Phase 3 Trial using TVEC, Talimogene Laherparepvec, which is an elegant approach to managing melanoma. The simple idea, and most great ideas are simple, is that you use a virus to penetrate specific cells, and then get the virus to do what it does best, multiply, and kill the cell.

Amgen describes TVEC as:

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumor tissue. Talimogene laherparepvec is injected directly into tumor tissue and then replicates until the membrane of the cancer cells rupture, thereby destroying the cells, in a process known as cell lysis. The virus that was contained in these cells is then released locally in the tumor tissue along with GM-CSF, a white blood cell growth factor that the virus is engineered to express. This is intended to lead to the activation of a systemic immune response to kill tumor cells throughout the body. 

 As is reported in GEN:

TVEC is based on a herpes simplex virus type 1 (HSV-1) that has been modified to selectively replicate in tumor cells without harming healthy cells. TVEC represents a new class of therapy against melanoma because it combines local with systemic effects against tumors. That effect is believed to be achieved through the functional deletion of two key genes (ICP34.5 and ICP47) from HSV-1, which deprives it of the proteins normally used for circumventing the body’s response to infections, followed by the addition of the human GM-CSF gene.

When injected directly into tumors, TVEC selectively replicates until the membrane of the cancer cells rupture or lyse, destroying these cells and releasing the viruses that have been replicated. The released viruses, in turn, invade more tumor cells—a cycle that continues until the weakened virus encounters healthy cells. During replication, TVEC also induces the tumor to produce GM-CSF—a white blood cell growth factor that attracts and activates the cells required for a systemic immune response.

This elegant approach selects a viral carrier which selects the melanoma cell and then enters it and replicates itself until the cell is killed off. This approach may have great applications in many other cancers.

Simply it works as follows:

Step 1 Virus is engineered to have attraction to a melanoma cell.

Step 2 The virus invades.

Step 3 The virus kills the targeted cell.

Nice idea and execution. Very interesting execution and great to follow up on. I tried something akin to this a few years ago on plant cells, TMV vector, with some success.