First, they need the DCVax-l unblinded results to see if a dent in unmethylated is possible with that immunotherapy. Dr. Bosch thinks the blinded data seem to point toward some effectiveness there.
For years, although the latest spore trial is only now in the planning works, Dr. Prins and Dr. Liau have known the ultimate DCVax-l combination would likely be DCVax-l + CI + CSF1R (odd-3397) + poly iclc.
So, what does this mean for DCVax-l?
If DCVax-l has some level of efficacy against unmethylated, the likelihood is the above combination will enhance that impact.
I’d personally guess the most important reason would be the addition of csf1r to DCVax, because it removes most immunotherapeutic suppressing cells from the equation in the brain. They know this, interestingly, because of experiments to treat concussion. CSF1R can temporarily remove almost all regulatory micro glia from the brain. Micro glia are a type of macrophage.
As you know, suppressive macrophage also often crowd into the tumor once CI + DCVax-l are administered. This sets up a war between suppressive forces versus therapeutic t-cells cells. CSF1R temporarily can, for whatever length of time it is administered, eliminate the tolerant/suppressive cells from the equation.
How will this theoretically help remove unmethylated tumor cells? Well, if DCVax-l is even slightly predisposed to efficacy against unmethylated, imagine what it can do if the immune system is stopped from trying to elicit tolerance to the unmethylated cells. Right, it’s basically giving DCVaxl charged t-cells more time to work unperturbed by suppressive forces.
This in turn probably makes CI safer to use in combination with DCVax-l, because it does not cause a massive rush of tolerance inducing cells, and thus the chance for rapid progression, which CI can otherwise cause, is mitigated.
I’ll leave a return discussion for poly iclcs role in the combo for another time.
