Overview of monoclonal antibodies, nanobodies, and antibody-based fragments and scaffolds directed at and modulating CXCR4 and ACKR3 function
| Antibody (Company) | Target | Format | Mechanism of Action | Indication | Phase | Reference |
|---|---|---|---|---|---|---|
| Ulocuplumab (Bristol-Myers Squibb) | CXCR4 | hIgG4 | CXCR4 inhibition, apoptosis induction | AML | Phase 1/2 ongoing (NCT02305563) | Kuhne et al. (2013), Kashyap et al. (2016) |
| WM | Phase 1/2 ongoing (NCT03225716) | |||||
| LY2624587 (Eli Lilly and Company) | CXCR4 | hzIgG4 | CXCR4 inhibition, apoptosis induction | Metastatic cancer | Phase 1 completed (NCT01139788) | Peng et al. (2016b, 2017) |
| PF-06747143 (Pfizer) | CXCR4 | hzIgG1 | CXCR4 inhibition, apoptosis induction, ADCC, and CDC | AML | Phase 1 terminated (NCT02954653) | Kashyap et al. (2017), Liu et al. (2017), Zhang et al. (2017) |
| hz515H7/F50067 (Pierre Fabre) | CXCR4 | hzIgG1 | CXCR4 inhibition, ADCC, and CDC | MM | Phase 1 | Broussas et al. (2016), Fouquet et al. (2018) |
| MEDI3185 (Medimmune) | CXCR4 | hIgG1mut | CXCR4 inhibition, apoptosis induction | Hematologic malignancies | Preclinical | Kamal et al. (2013), Peng et al. (2016a), Schwickart et al. (2016) |
| IgGX-auristatin | CXCR4 | IgG, ADC | Auristatin-mediated cytotoxicity | Metastatic cancer | Preclinical | Kularatne et al. (2014) |
| 238D2, 238D4 (Ablynx) | CXCR4 | Nb | CXCR4 inhibition, anti-HIV activity, HSC mobilization | — | Preclinical | Jähnichen et al. (2010) |
| 10A10 | CXCR4 | Nb | CXCR4 inhibition | WHIM syndrome | Preclinical | de Wit et al. (2017) |
| VUN400-402 | CXCR4 | Nb | CXCR4 inhibition, anti-HIV activity | — | Preclinical | Van Hout et al. (2018) |
| VUN400-402 | CXCR4 | Nb-Fc | CXCR4 inhibition, anti-HIV activity, ADCC, and CDC | — | Preclinical | Bobkov et al. (2018b) |
| AD-114 (AdAlta) | CXCR4 | i-body | CXCR4 inhibition, anti-HIV activity | IPF | Preclinical | Griffiths et al. (2016, 2018) |
| bAb-AC1, bAb-AC4 | CXCR4 | Antibody scaffold | CXCR4 inhibition | — | Preclinical | Liu et al. (2014) |
| NB1-3 (Ablynx) | ACKR3 | Nb | ACKR3 inhibition | Head and neck cancer | Preclinical | Maussang et al. (2013) |
| X7Ab | ACKR3 | scFv-Fc | ACKR3 inhibition, ADCC, CDC, and ADCP | GBM | Preclinical | Salazar 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.