I routinely remove the caches with CleanMyMac3, so it cannot be those.
By careful with CleanMyMac 3. I have tested it on a test library and had afterward a lot of broken links. I would not let it touch my library. Photos could no longer find the originals for many photos and I had to restore the library from a backup.
Yes, Photos is keeping a lot of working copies, but for a good purpose. All photo applications by Apple are supporting a lossless workflow (Aperture, iPhoto, Photos). If you edit a photo you can revert it to the original version, each adjustment individually. The original image file is always preserved as it is, so we do not have to manage the originals on or own. And the thumbnails are created to make the browsing faster and to make the photos available to other applications in the media browser. I am willing to sacrifice the extra 25% space for cached data to have a faster and more responsive Mac. Without the extra thumbnails for browsing it would be a pain to switch between albums, because photos would have to create the thumbnails on demand and I would be always seeing the beach ball spinning. For a large library this would be horribly slow.
If you do not like the lossless workflow, you would be better off by managing the photos yourself in folders in the Finder.
I am only keeping my smaller library with the favorites and the most recent projects on my system drive and the archive with all photos on an external drive. And I only clean caches, if something is crashing and I suspect corrupted files in a cache. Then I remove the cache for the application that is having trouble. Otherwise I leave the caches alone. Clearing the caches will just force the app to waste time by recreating the cached content.