Antibody-modified conduits for highly selective cytokine elimination from blood

Abstract

Cytokines play an important role in dysregulated immune responses to infection, pancreatitis, ischemia/reperfusion injury, burns, hemorrhage, cardiopulmonary bypass, trauma, and many other diseases. Moreover, the imbalance between inflammatory and antiinflammatory cytokines can have deleterious effects. Here, we demonstrated highly selective blood-filtering devices - antibody-modified conduits (AMCs) - that selectively eliminate multiple specific deleterious cytokines in vitro. AMCs functionalized with antibodies against human vascular endothelial growth factor A or tumor necrosis factor α (TNF-α) selectively eliminated the target cytokines from human blood in vitro and maintained them in reduced states even in the face of ongoing infusion at supraphysiologic rates. We characterized the variables that determine AMC performance, using anti-human TNF-α AMCs to eliminate recombinant human TNF-α. Finally, we demonstrated selective cytokine elimination in vivo by filtering interleukin 1 β from rats with lipopolysaccharide-induced hypercytokinemia.

Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19

“…Novel approaches to try to protect the host from deleterious effects of imbalance between pro-and anti-inflammatory mediators include blood-filtering devices such as antibodymodified conduits (AMCs) that can remove specific cytokines in vitro. AMCs that use antibodies against human vascular endothelial growth factor A (VEGF-A) or TNF-α are able to remove specific cytokines from the blood in vitro [41].…”

Biparatopic Nanobody-Based Immunosorbent for the Highly Selective Elimination of Tumor Necrosis Factor-α

“…18,19 McAlvin et al used antibodies to modify cibdyurs for the elimination of TNF-α from the blood. 20 Nevertheless, the adoption of antibody-based immunosorbents in commercial and industrial settings is impeded by the expensive "Cost of Good", long fermentation times, and insufficient stability of conventional antibodies. 21,22 Nanobodies (Nbs), the smallest antibody fragments (average 13 000−15 000 Da) with antigen affinity, are the variable domains of the heavy chain of heavy chain-only antibodies (VHH) derived from camelids.…”

“…However, TNF-α elimination by CytoSorb still remains below 50% because of its low concentration (mostly <1000 ng/L in sepsis) and large size (51 kDa). ,− Furthermore, the nonspecific adsorbents leading to simultaneous removal of beneficial substances (therapeutic antibiotics, clotting factors, etc.) necessitate additional monitoring of drug levels and adjustments in dosage, causing additional workload for healthcare providers. − To enhance the specific removal of TNF-α, Weber et al and Dileo et al constructed immunosorbents with antibodies as high-affinity ligands. , McAlvin et al used antibodies to modify cibdyurs for the elimination of TNF-α from the blood . Nevertheless, the adoption of antibody-based immunosorbents in commercial and industrial settings is impeded by the expensive “Cost of Good”, long fermentation times, and insufficient stability of conventional antibodies. , …”