To me the biggest problem is security of control
No, the biggest problem, and the one that will kill it stone dead, is money. Who is going to pay the billions and squillions it would take to get a pilotless airliner certified?
The airlines? No, they never asked for one
Boeing/Airbus? No, they don't have customers lined up and their regular buyers would crucify them if they thought they were funding blue sky research like this and passing the costs on to their bread-and-butter products.
Governments? Come off it, they want UAVs to do their dirty work, end of story.
At the end of the day, who wants pilotless airliners, and why? There are only two conceivable reasons, safety and economics. The safety case will never be proved, and the economics (fuel more expensive = crew relatively less so) will never overcome passenger resistance.
Not in my lifetime of the one after, anyway. maybe when the Chinese take over the world they will do it ther way, money no object, anything is possible