Dose-limiting toxicity liabilities caused by on-target off-tumor binding limit the efficacy of immune agonists. Mabimmune’s Reverse Translational Medicine (RTM™) human monoclonal antibodies are selected for conditional target binding in the tumor microenvironment, but not in other tissues. Generated in humans and cloned directly from human genes, RTM™ antibodies have fully human germline sequences and lower toxicity, off-tumor sinking, and immunogenicity risks compared to other antibody classes.