| Spoken like someone who hasn't been following the Kite trials... Also of note: just like good ol' mAbs, you need a target for CAR-T cells. And BiTEs, and BiKEs, and what have you. Also also of note: the approaches that took pediatric ALL and adult APL (among others) from 5-10% survival to 90-95% survival weren't single pronged. (Good thing, too; I've seen patients who seemed ideal for CAR-T die when their malignancy outran the engineered cells) The majority of progress in real-world outcomes has arisen from combination or sequential therapies, incrementally improved to decrease toxicity and maximize efficacy. Which is to say, incrementally advanced. Last: per the above, you can use the two together. If a tumor is actively suppressing T cells, it isn't going to dissolve from CAR-T cells without a fight. There are additional tactics useful for "priming" the immune system, but in the end I don't see a lot of solid tumors melting away in trials of CAR-T cells (feel free to correct me). Do take a look at the Kite trials and how they're structured. When you have to condition a patient with fludarabine to hit outcomes (at all) that's not a wonder drug. It's another tool in the toolbox. A necessary and useful tool, but a tool, not a magic wand. |
I work on immunosenescence and immune stimulation (the real thing) in oncology, and I happen to believe that we do many patients a disservice by nuking their immune systems with chemo and then relying on things like TKIs or BiTEs to pick up the mess. But it's also important to keep in mind that Gleevec alone didn't get rid of CML, and the way ALL and APL were managed up to 95% cure rates is by adding a little poison (As2O3, methotrexate, etc.) to the brew (asterisk) to finish things off. It's a delicate balance. I think it always will be.
(asterisk: ok more like a metric fuckload of poisons for ALL. But the real trick is "resurrecting" the patient with leukovorin after folate starvation essentially kills them.)
http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car...
Look up the SuperMAB saga for more cautionary tales. Plenty of people have died from chemo and immunosuppression too (nobody benefits from lungs full of aspergillus and a gut full of C. diff). If it were easy, somebody would have figured it out already :-)