CA9 and neoplasm: In order to investigate the ability of the novel CAIX-targeting ISAC 3 to accumulate in tumors and deliver the immunomodulating R848 payload, ex vivo mass spectrometry-based biodistribution studies in tumor-bearing mice were performed, following a similar protocol reported for MMAE conjugates (Zana et al., 2022) and specifically aimed at i) the detection of the free, released R848 and ii) total antibody quantification, regardless of its chemical functionalization with the linker-drug module.