Leadartis announces the publication "An Fc-free EGFR-specific 4-1BB-agonistic trimerbody displays broad anti-tumor activity in humanized murine cancer models without toxicity” in Clinical Cancer Research

02-04-2021

https://clincancerres.aacrjournals.org/content/early/2021/03/29/1078-0432.CCR-20-4625

Although systemic administration of anti-4-1BB-agonistic IgGs, have shown promise in early clinical studies have not completed clinical development due to their severe hepatotoxicity. Here  we demonstrate that a humanized EGFR-specific 4-1BB-agonistic trimerbody exhibits potent anti-tumor activity in vivo, without hepatotoxicity, in a wide range of human tumors including colorectal and breast cancer cell-derived xenografts, and non-small-cell lung cancer patient-derived xenografts associated with increased tumor-infiltrating CD8+ T cells. The combination of the trimerbody with a PD-L1-blocker resulted in tumor regression in humanized mice bearing aggressive triple-negative breast cancer.

Our results demonstrate the non-toxic broad anti-tumor activity of humanized Fc-free tumor-specific 4-1BB-agonistic trimerbodies and their synergy with checkpoint blockers, which may provide a way to elicit responses in most cancer patients while avoiding Fc-mediated adverse reactions.

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