Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Fractalkine (FKN) and its solo receptor CX3CR1 are deeply involved in the pathogenesis of rheumatoid arthritis (RA). FKN is expressed on vascular endothelium, while CX3CR1 is expressed on peripheral blood leukocytes such as monocytes/macrophages, NK cells, effector CD8+ T cells and a minor fraction of CD4+ T cells. E6011, a novel humanized anti-FKN monoclonal antibody (mAb), is under clinical development in RA. In order to continuously assess the E6011 pharmacodynamics by monitoring the alteration of peripheral blood immune cells, including CX3CR1-expressed cell populations, a series of multi-color flow cytometry (FCM) was conducted before and during the course of the E6011 treatment of active RA patients in phase 2 clinical trial.
Methods: Immuno-phenotypic changes were explored by FCM during the E6011 administration in 190 Japanese RA patients with inadequate response to MTX (NCT02960438). Patient’s peripheral blood were drawn into fixative tube (Cyto-Chex® BCT, Streck) at each clinics and thereafter transported to the FCM facility at KAN Research Institute. Inc. within 30 hours after the blood collection to operate the FCM analysis by standardized method. Immuno-phenotyping was carried out by multi colors flow cytometry (BD FACSCantoIITM, BD LSRFortessaTM, BD Biosciences).
Results: Based on these determined conditions, CX3CR1 expression on monocytes, NK cells and a part of CD8+ and CD4+ T cells were confirmed in this method. Interestingly, during the E6011 treatment, the proportion of CD16+ monocytes, which highly express CX3CR1 within whole monocytes, were significantly decreased at 2 week after initial treatment from the baseline (E6011 : p < 0.001, placebo: p > 0.48) and sustained up to 24 week, while that of CD16– monocytes were increased. The reduction of the proportion of NK cells, CD4+ and CD8+ T cells were not observed, but in some certain populations like CX3CR1-expressed CD56+CD16+ NK cells and terminal differentiated effector CD8+ T cells, the percentage of these populations tended to increase from the baseline at 2 week and kept increasing up to 24 week by the E6011 treatment.
Conclusion: Our results indicated that the reduction of CD16+monocytes after initial treatment might be a sensitive pharmacodynamic marker of E6011 exposure, possibly reflecting mechanism of action of E6011, since the CD16+monocytes are the most abundant CX3CR1+ cell population in peripheral blood.
To cite this abstract in AMA style:Yamada T, Kakuta J, Fusaoka-Nishioka E, Ito J, Yasuda N, Kawano T, Imai T. Immuno-Phenotypic Analysis of Peripheral Blood Mononuclear Cells in Rheumatoid Arthritis Patients Treated with E6011, a Humanized Anti-Fractalkine Monoclonal Antibody [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/immuno-phenotypic-analysis-of-peripheral-blood-mononuclear-cells-in-rheumatoid-arthritis-patients-treated-with-e6011-a-humanized-anti-fractalkine-monoclonal-antibody/. Accessed September 25, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immuno-phenotypic-analysis-of-peripheral-blood-mononuclear-cells-in-rheumatoid-arthritis-patients-treated-with-e6011-a-humanized-anti-fractalkine-monoclonal-antibody/