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
1Transplant Immunology Laboratory, Cedars Sinai Medical Center, Los Angeles, CA, 2Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA
Meeting: 2021 American Transplant Congress
Abstract number: 167
Keywords: B cells, Kidney transplantation, Natural killer cells, Sensitization
Topic: Clinical Science » Kidney » Kidney Immunosuppression: Desensitization
Session Information
Session Name: Kidney Desensitization/KPD
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 6, 2021
Session Time: 6:00pm-7:00pm
Presentation Time: 6:05pm-6:10pm
Location: Virtual
*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 | ||||
| M% | L% | T3% | B% | NK% | Treg% | Tfh% | |
| 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) |
| Pre-Dara | 6.2 | 27.8 | 83.6 | 5.0 | 5.5 | 2.1 | 0.33 |
| 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 November 21, 2024.« Back to 2021 American Transplant Congress