“Better late than never” is an oldie but goodie.
If we’ve said that line once, we’ve said it 100 times about lead EpicentRx therapy, AdAPT-001, plus an immune checkpoint inhibitor (ICI). That’s because AdAPT-001 and the ICI are almost always (unfashionably) late to the anticancer response party. Not days or weeks late, but several months late, sometimes as much as 6 months late. In the meantime, tumors may get larger, which can scare patients, and often does, if they don’t take off on vacation first. More than once, buoyed by how much better they feel, patients have skipped town to parts unknown without so much as a by-your-leave to their physicians or to the cancer center. And more power to them for that.
The lesson with AdAPT-001 plus an ICI is “don’t believe your lyin’ eyes”. When scans show larger tumors and/or more tumors, but patients feel better, or at the very least not worse, to the extent that travel becomes possible, it doesn’t take an advanced degree to know that something is up in a good way. We have a name for this divergence between scans and symptoms with treatments like AdAPT-001 — false progression or pseudoprogression.
When AdAPT-001 infects cancer cells, it expresses a transforming growth factor beta (TGFβ) trap that binds to and eliminates the immunosuppressive cytokine, TGFβ, which activates an emergency Bat Signal for immune cells to follow. So, what happens with pseudoprogression, then, is that immune cells, having heeded the call to arms, rush in and inflame the tumors, which, to all appearances, are worse. The massive “Clean Up on Aisle 5” effort that must occur before tumor reduction can take place happens over several months, which is why responses with AdAPT-001 + an ICI are delayed. Hence, pseudoprogression refers to the initial increase of tumor burden because of immune cell activation and infiltration followed by subsequent regression as these immune cells go to work on the cancer cells and, simultaneously, undertake a massive cleanup effort.
Still, it would be preferable if AdAPT-001 and an ICI would skip over the pseudoprogression part and go straight to tumor reduction.
But, hey, as we say time and time again, “we’ll take it” and “better late than never”.