ArticleClinical & translational immunology2026
Enhanced Fc and complement activity of Fc-modified avelumab boosts anti-tumor activity but promotes NK cell fratricide.
Article in Clinical & translational immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: The anti-PD-L1 antibody avelumab has demonstrated efficacy across multiple cancer types. Avelumab primarily blocks the PD-1/L1 immune checkpoint, while inducing antibody-dependent cellular cytotoxicity (ADCC) from CD16a Methods: Comparisons between the wild-type avelumab and modified 'AveFc5M' were carried out to assess the impacts of introduced mutations on PD-L1 blockade, ADCC induction and complement-dependent cytotoxicity (CDC) induction. To assess ADCC, a range of PD-L1 Results: Both antibodies exhibited equivalent PD-L1 blocking activity. Notably, the modified AveFc5M displayed significantly enhanced ADCC across diverse tumor cell-effector cell combinations. Fc mutations also conferred the ability to mediate complement-dependent cytotoxicity (CDC) against a PD-L1 Conclusion: These findings demonstrate that Fc engineering of avelumab can substantially augment ADCC and CDC activity against PD-L1
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