Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis

J Immunother. May-Jun 2005;28(3):212-9. doi: 10.1097/01.cji.0000155050.03916.04.

Abstract

PRO70769 is a humanized IgG1 monoclonal antibody against the CD20 molecule that is present on normal and malignant B cells. PRO70769 is being evaluated for treatment of B-cell-mediated diseases and is in a phase 1 trial for rheumatoid arthritis. As part of the preclinical toxicology evaluation, B-cell depletion profiles and safety of PRO70769 were assessed in cynomolgus monkeys. Animals were administered drug (IV) on days 1 and 15 with 10, 50, or 100 mg/kg PRO70769 and killed 2 weeks after the second dose and after a 3-month recovery period. In a parallel study, animals were not necropsied but instead were retreated with a second cycle of PRO70769 administered under an identical regimen. PRO70769 suppressed B cells in the blood to undetectable levels and significantly reduced B cells in lymphoid tissues. Splenic B cells were depleted to a greater extent compared with lymph node B cells. A second cycle of treatment resulted in a greater extent of depletion in lymphoid tissues compared with the depletion observed after one cycle of treatment; however, residual B cells in lymphoid tissues were still detectable, even at the highest dose. The rate of B-cell recovery in peripheral blood appeared similar between one and two cycles of treatment. Upon depletion there was a change in the profile of lymph node B-cell subsets. After recovery, B-cell subsets were reconstituted to normal levels. Depletion of CD20-expressing cells and lymphoid follicular atrophy were the only treatment-related effects.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20 / immunology*
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Lymph Nodes / cytology
  • Lymphocyte Depletion*
  • Macaca fascicularis
  • Spleen / cytology

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Immunoglobulin G
  • PRO70769 monoclonal antibody