Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity

Significance Regulatory T cells (Tregs) protect cancer cells from immune attack. Tregs express CD25 on their surface and can be killed by antibodies and immunoconjugates targeting CD25. These agents have not been effective in controlling tumor growth, probably because they also kill cytotoxic CD8 T cells expressing CD25 that are needed for antitumor activity. To overcome these deficiencies, we have directly injected tumors with a potent anti-CD25 immunotoxin, 2E4-PE38, that kills CD25-expressing Treg cells in the tumor, causes injected and distant tumors to regress, and induces antitumor immunity. Because 2E4-PE38 is present at very low concentrations in the blood, it does not kill CD25-expressing cells at distant sites. This strategy could be employed for treating tumors in people.