Prime Time

For all the hype about PD-1 and PD-L1 checkpoint inhibitors its easy to forget that they don't work for most patients. The way forward in reaching the 70-80% of patients that do not respond to single agent immunotherapies is through combinations. Genentech are front and centre in the race to find the most compelling scientifically based combinations. So what are they and other players looking for and why might Imugene find itself in the box seat!

In as much as the PD-1 and PD-L1 pathways are important there are other additional immunosuppressive mechanisms within the tumor micro-environment. One that keeps popping up is T regulatory cells or Treg, otherwise referred to as tumor bodyguards. Inhibitory mechanisms like Treg limit the efficacy of checkpoint inhibitors and provide targets for combination therapy. The important qualification, however, is how to block or inhibit Treg without a significant increase in toxicity e.g. one common strategy is chemotherapy.

Imugene presentations make the point that HER-Vaxx can influence the micro-environment and suppress Treg. Its just one of the things that it does. If the Phase 1b/2 trial validates the role of HER-Vaxx in T regulatory inhibition it will be big news, possibly really big news if the level of Treg suppression is increased with the revamped formulation. To top it all off, HER-Vaxx has an enviable safety profile.

Priming the immune system in order to improve the activity of checkpoint inhibitors is one of the key objectives in combination therapy. If Imugene's upcoming trial can demonstrate improved Treg suppression it could be prime time.