Overview of monoclonal antibodies, nanobodies, and antibody-based fragments and scaffolds directed at and modulating CXCR4 and ACKR3 function

Antibody (Company)TargetFormatMechanism of ActionIndicationPhaseReference
Ulocuplumab (Bristol-Myers Squibb)CXCR4hIgG4CXCR4 inhibition, apoptosis inductionAMLPhase 1/2 ongoing (NCT02305563)Kuhne et al. (2013), Kashyap et al. (2016)
WMPhase 1/2 ongoing (NCT03225716)
LY2624587 (Eli Lilly and Company)CXCR4hzIgG4CXCR4 inhibition, apoptosis inductionMetastatic cancerPhase 1 completed (NCT01139788)Peng et al. (2016b, 2017)
PF-06747143 (Pfizer)CXCR4hzIgG1CXCR4 inhibition, apoptosis induction, ADCC, and CDCAMLPhase 1 terminated (NCT02954653)Kashyap et al. (2017), Liu et al. (2017), Zhang et al. (2017)
hz515H7/F50067 (Pierre Fabre)CXCR4hzIgG1CXCR4 inhibition, ADCC, and CDCMMPhase 1Broussas et al. (2016), Fouquet et al. (2018)
MEDI3185 (Medimmune)CXCR4hIgG1mutCXCR4 inhibition, apoptosis inductionHematologic malignanciesPreclinicalKamal et al. (2013), Peng et al. (2016a), Schwickart et al. (2016)
IgGX-auristatinCXCR4IgG, ADCAuristatin-mediated cytotoxicityMetastatic cancerPreclinicalKularatne et al. (2014)
238D2, 238D4 (Ablynx)CXCR4NbCXCR4 inhibition, anti-HIV activity, HSC mobilizationPreclinicalJähnichen et al. (2010)
10A10CXCR4NbCXCR4 inhibitionWHIM syndromePreclinicalde Wit et al. (2017)
VUN400-402CXCR4NbCXCR4 inhibition, anti-HIV activityPreclinicalVan Hout et al. (2018)
VUN400-402CXCR4Nb-FcCXCR4 inhibition, anti-HIV activity, ADCC, and CDCPreclinicalBobkov et al. (2018b)
AD-114 (AdAlta)CXCR4i-bodyCXCR4 inhibition, anti-HIV activityIPFPreclinicalGriffiths et al. (2016, 2018)
bAb-AC1, bAb-AC4CXCR4Antibody scaffoldCXCR4 inhibitionPreclinicalLiu et al. (2014)
NB1-3 (Ablynx)ACKR3NbACKR3 inhibitionHead and neck cancerPreclinicalMaussang et al. (2013)
X7AbACKR3scFv-FcACKR3 inhibition, ADCC, CDC, and ADCPGBMPreclinicalSalazar et al. (2018)
  • ADC, antibody-drug conjugate; ADCP, antibody-dependent cellular phagocytosis; AML, acute myeloid leukemia; GBM, glioblastoma; hIgG, human IgG; HSC, hematopoietic stem cell; hzIgG, humanized IgG; IgG1mut, triple mutant lacking ADCC and CDC; IPF, idiopathic pulmonary fibrosis; Nb-Fc, nanobody fused with Fc domain from IgG1; scFv, single-chain variable fragment fused with Fc domain from IgG1; WHIM, warts, hypogammaglobulinemia, infections, and myelokathexis; WM, Waldenström’s macroglobulinemia.