Do it!
I've always thought about doing this but the problem I run into is making the box (think earth roamer fiberglass box). Your idea is actually a world better than mine because the box is already furnished and all the specifics are already there - all is needed is some re-doing and modification.
I'm in the process of stretching my f350 crew cab to have a 12ft bed, dump bed, and a box... All of which, would be able to slide on and off. Wouldn't mind a winnebago box mated up to my truck.
The box to truck connection is tricky. I dreamed up an idea on how to do it. Can't really show you b/c I don't have it drawn down but picture this: Your box will have a donut cushion on it, the truck will have the female donut shape. Once you slide on the box, it will be a perfect seal. I use to have a photo of it from another truck and it's similar to that.