Yeah, there's also possibly a crowding effect (mentioned in the context of 10 million cell doses doing worse than 1 million cell doses), but I didn't mean increasing the size of the early doses so much as the frequency of dosing after the first few (when it spreads out as far as 6 months instead of 2 weeks), and the maximum follow-up shots allowed for in the protocol (28 months, which is about half what can be produced and preserved).
It's even more of a concern with the direct trial than with the lysate trial (but understandable because this one is first-in-human and they're playing nice with the regulators) - in this case, aiming for tumor regression (and maximum effect on remote satellite tumors that aren't themselves as injectable), I would have chosen weeks 0/1/2/4/8/16/32 (if still applicable) as opposed to the current trial's 0/1/2/16/32. If a requirement is to use only five cycles, considering the state and prognosis of the indication and again the goal of regression (very different from the dcvax-l context where duration matters), then I'd do 0/1/2/4/8 and forget about the final two doses which might not be applicable anyway. If it's working well, the largest tumors will be shrinking before week 16 to a point where you can't inject more; you need a way to maximize systemic (as opposed to local) response and sustain it for as long as possible. If it's not working well, more frequent (not larger) doses earlier may help, there's no point worrying about saving for week 32 when you're just trying to live past 16, and because this is just optimized DCs without using extracted tumor, you can always pull more if you run out. Keep in mind that while Triozzi's cultured DCs were supposedly less potent, he did manage to successfully cram 30 million of them (much more than the company's maximum dose size) in at a time to great effect, so I'm not too worried about crowding.
That said, I'm not ignoring the fact that these guys know their own technique and what they're doing far better than I do, so I'm sure it's well-reasoned, just concerned is all.
