The DMCA takedown provisions are a safe harbor against legal liability -- compliance protects a host against legal liability they would otherwise have to a copyright holder for copyright violations. Implicitly, they are backed by the threat that, if the receiver fails to comply, they will be subject to a lawsuit for copyright infringement.

If you are sending DMCA takedown notices and they are being brushed off, you probably are at the point where you need to talk to a lawyer