Amivantamab (JNJ-61186372) is an EGFR/cMet bispecific low fucose antibody that recently received breakthrough therapy designation and is being testing clinically in NSLC patients. In this preclinical study, Vijayaraghavan and colleagues demonstrated that interaction of the Fc domain of amivantamab with monocytes or macrophages induces trogocytosis leading to EGFR and cMet receptor downmodulation and tumor cell death. In addition, they found that macrophages were required for amivantamab anti-tumor efficacy in vivo. Thus, this represents a novel Fc-dependent mechanism of action for amivantamab, and highlights trogocytosis as a key mechanism to exploit in designing new antibody-based cancer therapies.
The deubiquitinase USP7 stabilizes the expression of multiple substrates important in tumor progression, such as MDM2, PIM2 kinase, and MYCN. Therefore, potent inhibitors of USP7 are highly desired. Ohol and colleagues report selective inhibitors of USP7 which impede its binding to ubiquitin and tested the inhibitors on a panel of 430 cancer cell...
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