Session Time: 6:00pm-7:00pm
Presentation Time: 6:05pm-6:10pm
*Purpose: Antibody-Mediated Rejection (ABMR), primarily mediated by B cells, plasma cells (PC) and antibodies (Ab), is an obstacle for successful transplantation in HS KTx Pts. Removal of those by Dara is a promising treatment for DES and ABMR. Here, we investigated the effect of Dara on immune cells (IC) in vitro and in a HS KTx Pt with Dara-DES.
*Methods: CD38 expression on IC in normal control (NC) whole blood, and IC numbers in NC PBMC incubated w/ Dara (0-500µg/ml, 0-48 hrs) were measured by flow cytometry. IC profiles pre- and post-Dara (1wk post-1st and 3rd, and 1M post-4th Dara) in a HS KTx Pt with DES w/plasma-exchange + IVIG followed by weekly Dara (16 mg/kg IVPB, ×4) were tested by flow cytometry. Ab-CD16-mediated NK cell (NK) response in Pt PBMC was tested by the modified allo-CFC where Pt PBMC was stimulated with Ab-coated allo-PBMCs followed by intracellular IFNγ+ NK detection.
*Results: 100% of monocytes (M), >90% of NK, 80% of B cells (B), 40-50% of T (T) cells expressed CD38. The CD38 expression level is the highest in PC and plasmablasts (PB), high in Breg, NK and M, and moderate in T and the remaining cells. After NC PBMC incubation w/ Dara, the number of M and all lymphocyte (L) cell subsets decreased at 24 & 48 hrs vs. 0 hr in a dose dependent manner. NK% in L significantly decreased, while T% & B% in L did not. A similar IC change was seen in the Dara-treated patient (Table 1); The number of M and all L cell subsets significantly decreased post-Dara. The NK% in L significantly decreased even at 1M post-4th Dara, while the change in T% & B% in L, and follicular T helper (Tfh)% and Treg% in CD4+ T (T4) was minimal. IFNγ+ cell% in NK in the modified allo-CFC decreased post-Dara (2.06, 2.32, 0.51 and 1.23, respectively), while those in NC PBMC tested as control at each time point showed similar NK response (24.8, 33.7, 31.5 and 34.9, respectively). Anti-HLA Ab Class I &II score reduced post-Dara from 619 to 513.
*Conclusions: Dara significantly reduced the number of M and L, especially NK, high CD38 expressing cells, and likely PC and PB as well as anti-HLA Ab decreased post-Dara. It also reduced Ab-CD16-mediated NK activation in Dara-treated Pt. This suggests possible utility of Dara for DES or ADCC-mediated ABMR treatment in HS KTx Pts.
|Cell% in Parent Cells||In Leukocytes||In L||In T4 Cells|
|Ref. Median (Range)||6.1(4.8 – 8.0)||36.2(24.9 – 53.5)||75.5 (62.3 – 83.4)||12.7(5.6 – 18.3)||9.4(6.2 – 20.7)||4.8 (3.4 – 7.1)||0.31 (0.14 – 0.61)|
|1wk post-1st Dara||5.8||14.0||84.5||6.5||2.4||2.8||0.25|
|1wk post-3rd Dara||4.8||11.4||88.1||5.0||3.1||1.3||0.10|
|1M post-4th Dara||4.3||16.8||92.2||3.0||1.6||1.5||0.32|
To cite this abstract in AMA style:Ge S, Chu M, Guzman ADe, Ortiz E, Vo A, Ammerman N, Jordan SC, Toyoda M. The Effect of Daratumumab (Dara, Humanized Anti-CD38 Monoclonal Antibody) on Immune Cells In Vitro and in a HLA-Sensitized Kidney Transplant Patient (HS KTx Pt) Desensitized (DES) with Dara [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/the-effect-of-daratumumab-dara-humanized-anti-cd38-monoclonal-antibody-on-immune-cells-in-vitro-and-in-a-hla-sensitized-kidney-transplant-patient-hs-ktx-pt-desensitized-des-with-dara/. Accessed August 3, 2021.
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