In preclinical studies using an MC38 colon carcinoma model, 4-1BB agonist therapy had little impact on tumor progression when administered early (less than 48 h after tumor implantation), while the combination of 4-1BB and anti-CTLA-4 together was effective even in established tumors (14 days after implantation) (55). Here, CTLA4 is linked to neoplasm.