Fc receptor engagement explains how anti-CD25 antibodies deplete intratumoral Tregs
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Anti-CD25 antibodies can eliminate regulatory T cells inside tumors, and the key is Fc receptor engagement, according to experts speaking on ImmuneZoom. A non-IL-2-blocking CD25 antibody achieved 100% complete regression as a single agent in inflamed tumors, and in a glioblastoma model it reached 100% complete regression when combined with an anti-EGFRv3 antibody, driven by IL-2-dependent CD8 expansion and IFN-gamma activation of macrophages. The clinical picture is harder: the humanized anti-CD25 RG6292 depleted Tregs in blood and was well tolerated, but intratumoral depletion was under 2-fold and unstable, which may explain its clinical failure. The team is now working on boosting Fc receptor activity in the tumor microenvironment to make depletion effective there.
Written by a model from the reports · updated 2 hours ago
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Experts on ImmuneZoom discuss how anti-CD25 antibodies deplete intratumoral Tregs through Fc receptor mechanisms. A non-IL-2-blocking CD25 antibody (NIB) achieved 100% complete regression as a single agent in inflamed tumors, and in a glioblastoma model, combined with an anti-EGFRv3 antibody, also reached 100% complete regression via IL-2-driven CD8 expansion and IFN-gamma activation of macrophages. The humanized anti-CD25 RG6292 depleted Tregs in blood and was well tolerated but achieved under 2-fold, unstable intratumoral depletion, which may explain clinical failure; the team now studies boosting Fc receptor activity in the tumor microenvironment.
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