Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa.

ABSTRACT: We analyzed the cross-reactivity of anti-drug antibodies (ADAs) against agalsidase-alfa and -beta from 49 patients with Fabry disease (FD) against the novel PEGylated enzyme pegunigalsidase-alfa (PRX-102). The affinity of purified anti-AGAL antibodies from pooled patient sera was significantly lower for PRX-102 compared to agalsidase-alfa and -beta (both p < 0.05). Pull-down experiments revealed the presence of masked epitopes on PRX-102, possibly due to PEGylation. ADA titers in serum (μg/mL) and corresponding inhibitory capacities against agalsidase-alfa and -beta were measured in male patients with FD, showing strong correlations (r² = 0.9978 and 0.4930, both p < 0.001). Affinities of ADAs of individual patients against PRX-102 (K_d: 3.55 ± 2.72 μmol) were significa

SUBMITTER: Lenders M 

PROVIDER: S-EPMC9379515 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature