TABLE 2

Summary of preclinical ADCs tested for rheumatic diseases

ADCIndicationAntibodyLinkerPayloadDARTesting StatusReference
Anti–TNF-GRM ADCChronic arthritis modelMurine anti-TNF mAbMaleimide-Gly-Ala-Ala linkerGRM4In vivo preclinicalStoffel et al., 2021; Hobson et al., 2022a,b
Anti–TNF-GRM ADCChronic arthritis modelAnti-TNF mAbA dipeptide-based (Ala-Ala) protease-cleavable
linker
GRM4In vivo preclinicalDragovich, 2022
Brentuximab vedotinChronic arthritis modelAnti-CD30 mAb (brentuximab)Valine-citrulline linkerMMAE4In vitro and vivo preclinicalMatsuhashi et al., 2020; Matsuhashi et al., 2022
Brentuximab vedotinRheumatoid arthritis with Hodgkin lymphomaAnti-CD30 mAb (brentuximab)Valine-citrulline linkerMMAE4Case reportVachhani et al., 2014; Nakazato et al., 2018; Ichikawa et al., 2020; Sekiguchi et al., 2020
Anti–IL-7R ADC (A7R-ADC-MMAE/SN-38)Autoimmune arthritis modelAnti–IL-7R mAb (A7R)Valine-citrulline linkerMMAE / SN-384-6In vivo preclinicalYasunaga et al., 2017
Tocilizumab-Alendronate ConjugateRheumatoid arthritisAnti–IL-6R mAb (tocilizumab)PDPH-PEG-NHSAlendronate1.14In vitro and vivo preclinicalLee et al., 2017
Anti–FcγRI-calicheamicin immunoconjugate (CD64-CaMi)Rheumatoid arthritisAnti-FcγRI (CD64) mAbN/ACalicheamicinN/AIn vitro preclinicalvan Roon et al., 2005
Anti–C5ab-C5 siRNA conjugate (anti-C5aR1 Ab-protamine-C5 siRNA conjugate)Chronic arthritis modelAnti-C5aR1 mAb (clone 20/70)ProtamineC5 siRNAN/AIn vitro and vivo preclinicalMehta et al., 2015
BDCA2-ADC
(DB-2304)
Systemic lupus erythematosusAnti-BDCA2 mAb (BIIB059)A cleavable linker containing maleimide tetrapeptideGC (DIMAC-HYX0449)4.07In vitro preclinicalLi et al., 2022; Liu and Oliver, 2023
Brentuximab vedotinSystemic lupus erythematosus with Hodgkin lymphomaAnti-CD30 mAb (brentuximab)Valine-citrulline linkerMMAE4case reportYohannan et al., 2022
Anti-CD74 ADC (anti–CD74-flu449)Autoimmune modelsAnti-CD74 mAb (recombinant anti-CD74 clone 011-pAF antibody)Pyrophosphate acetal linkerGRM (fluticasone propionate)≥1.7In vitro preclinicalBrandish et al., 2018
α-hCD70-conjugates (aCD70-8a,aCD70-8b)Autoimmune modelsα-Human CD70
antibody
Phosphate modified cathepsin B linkersBudesonide1.9In vitro preclinicalKern et al., 2016)
Anti-CD163 ADCChronic models of
inflammation
Anti-CD163 mAb (Ed-2)Hemisuccinate linkerDexamethasone4In vitro and vivo preclinicalGraversen et al., 2012
Dexamethasone- anti-E-selectin immunoconjugate (Dexa–AbhEsel conjugate)Chronic models of
inflammation
Mouse antihuman E-selectin antibody (H18/7)Succinate linkerDexamethasone2In vitro preclinicalAsgeirsdóttir et al., 2003
Anti–CD11a-PDE4 inhibitor ADCChronic models of
inflammation
A human αCD11a antibody (based on efalizumab clone hu1124)PEG4-Phe-LysPDE4 inhibitor GSK2560662In vitro and vivo preclinicalYu et al., 2016
  • FcγRI, Fc γreceptor I; GC, glucocorticoid; N/A, not available; PDPH-PEG-NHS, 3-(2-pyridyldithio)propionyl hydrazide–poly(ethylene glycol)–N-hydroxysuccinimide.