Effect of Two Anti-CD20 Abs on B Cell Depletion and Reconstitution in Non-Human Primates.
1Dept. of Surgery, University of Maryland, School of Medicine, Baltimore, MD
2MassBiologics, University of Massachusetts Medical School, Boston, MA
Meeting: 2017 American Transplant Congress
Abstract number: C13
Keywords: Antibodies, B cells, FACS analysis
Session Information
Session Name: Poster Session C: Antibody and B Cell
Session Type: Poster Session
Date: Monday, May 1, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: B lymphocytes play a central role in host immunity, including antibody elaboration and antigen presentation, and B-cell depletion is being explored to modulate alloimmunity. Rituximab does not consistently or durably deplete B cells in non-human primates (NHP). Here we investigate the efficacy of two new anti-CD20 antibodies, CD20R1V1 and CD202B8R1 in which the CDRs of rituximab were grafted into a native rhesus IgG1 to mediate B cell depletion in 2 NHP species.
Methods: Two Cynomolgus heart allograft recipients each received CD20R1V1 (20mg/kg weekly for 4 doses) and either anti-CD28 (FR104) or anti-CD40 (2C10R4), neither of which significantly deplete B-cells. Two Rhesus each received one dose of CD202B8R1 (50 mg/ml). Immunophenotyping of CD19+ CD20+ B cells was performed at intervals on PBL and lymph node by flow cytometry to quantify the frequency of switched memory (Sm: IgD–CD27+); unswitched memory (USm: IgD+CD27+); naïve (N: IgD+CD27–CD38+IgMint) and transitional B cells (Tr: IgD+CD27–CD38hiIgM+).
Results: All monkeys exhibited rapid efficient B cell depletion in peripheral blood that was sustained for 42-56 days [Figure 1, top panel]. USm and Sm depletion was relatively durable. A Tr phenotype predominated as B cells reappeared in PBL. B cell depletion in lymph nodes (LN) was incomplete particularly with the CD20R1V1 regimen (30-60% at D14), but was more profound with the CD202B8R1 regimen (100% at D14, ~70% at D28) [Figure.1, bottom panel] 
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Conclusions: Both aCD20 reagents efficiently deplete naïve and memory peripheral blood B cells for about one month, with incomplete efficacy and shorter duration of effect in LN. These data will inform design of future studies to evaluate the correlation between aCD20 treatment efficacy and relative efficiency and duration of B cells depletion in various immune compartments.
CITATION INFORMATION: Sun W, O'Neill N, Zhang T, Braileanu G, Reimann K, Pierson R, Azimzadeh A. Effect of Two Anti-CD20 Abs on B Cell Depletion and Reconstitution in Non-Human Primates. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Sun W, O'Neill N, Zhang T, Braileanu G, Reimann K, Pierson R, Azimzadeh A. Effect of Two Anti-CD20 Abs on B Cell Depletion and Reconstitution in Non-Human Primates. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/effect-of-two-anti-cd20-abs-on-b-cell-depletion-and-reconstitution-in-non-human-primates/. Accessed November 21, 2024.« Back to 2017 American Transplant Congress