Sharpie, glad the translation attempt helped. Thanks for posting the original conversation between Allison and Moss — it inspired me to dig a little deeper on checkpoint inhibitors. The whole conversation is very worthwhile, even though it just touches on very promising topics before jumping off on other tangents. A lot of interesting ideas there — I need to listen again and take notes!
The link to Dr Liau where she mentioned DC-Vax turning “cold” tumors “hot” points to the prospect of carefully controlled activation of dendritic cells being a key component of immunotherapy. It’s something that Allison mentions later in the conversation with Moss — ie, some tumor types are naturally cold, for example, pancreatic cancer.
He mentions at around 41 minute mark:
“If you have a cold tumor, checkpoint blockers aren’t going to do you any good because there’s no T-cells there,” although he later mentions that Ipilimubab (CTLA-4 checkpoint inhibitor) does help with getting t-cells into the tumor as well, while PD-1 inhibitors don’t.
However, PD-1 is then upregulated in the tumor that is newly infiltrated by T-cells, so they’re trying to use both types of checkpoint inhibitors together, at lower doses to avoid the additive toxicity. If we used DC-Vax-L, instead of Ipi, to turn cold tumors hot, we could avoid the additive toxicity of multiple checkpoint inhibitors.
One thing Allison mentions is that doctors are getting better at managing the side effects, given all the experience they’ve gained in the past few years. (Cue Longfellow — let’s get the real lowdown on adverse effects!).
There are many paths forward to optimization of immunotherapy. I believe direct manipulation of dendritic cells will play an important role. Long NWBO!
Thanks for the additional links!
