Certainly there are success stories when so much effort is put forward. But look at all the things even Imbruvica does in addition to helping treat cancer [1].
If you want to fix MCL you figure out how to engineer a genetic payload that targets B-cells IFF they express particular genes, and reengineer those cells' genomes to either no longer reproduce abnormally, or shut them down. You do NOT covalently turn off an entire class of kinases in the ENTIRE body...
And that's the success story. Antibodies are just the tip of the protein-iceberg. They're the 'same things as a small molecule' but in protein form - baby steps into a whole new world. Sure, they can bind to stuff tightly, but if that (alone) is what you're aiming for, then they're not being used to try to fix the problem or engineer a way to the solution. There's lots more that we could do if we started actually engineering the proteins and their interactions, and delivering them in directed ways. We have access to those primitive engineering tools, but instead of focusing on those nascent tools, we're polishing up the old hammer.
If you want to fix MCL you figure out how to engineer a genetic payload that targets B-cells IFF they express particular genes, and reengineer those cells' genomes to either no longer reproduce abnormally, or shut them down. You do NOT covalently turn off an entire class of kinases in the ENTIRE body...
And that's the success story. Antibodies are just the tip of the protein-iceberg. They're the 'same things as a small molecule' but in protein form - baby steps into a whole new world. Sure, they can bind to stuff tightly, but if that (alone) is what you're aiming for, then they're not being used to try to fix the problem or engineer a way to the solution. There's lots more that we could do if we started actually engineering the proteins and their interactions, and delivering them in directed ways. We have access to those primitive engineering tools, but instead of focusing on those nascent tools, we're polishing up the old hammer.
[1] https://en.wikipedia.org/wiki/Ibrutinib#Adverse_effects