Development of Novel Mouse Monoclonal Antibodies Against Human CD19

Monoclon Antib Immunodiagn Immunother. 2020 Apr;39(2):45-50. doi: 10.1089/mab.2020.0003.

Abstract

CD19 is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is expressed in normal and neoplastic B cells, and it modulates the threshold of B cell activation for amplifying B cell receptor signaling. Blinatumomab (a CD3-CD19-bispecific T cell-engaging antibody) and tisagenlecleucel (genetically modified T cells that express a CD19 chimeric antigen receptor [CART-19]) provide significant benefits for patients with CD19-positive relapsed or refractory B cell malignancies. In this study, we first employed the Cell-Based Immunization and Screening (CBIS) method to produce anti-CD19 monoclonal antibodies using CD19-overexpressing cells for both immunization and screening. One established clone-C19Mab-1-proved to be useful in flow cytometry assays against lymphoma cell lines, such as BALL-1, P30/OHK, and Raji. Second, the extracellular domain of CD19 was immunized into mice, and enzyme-linked immunosorbent assays were performed for the first screening. One established clone-C19Mab-3-was determined to be useful for Western blotting and immunohistochemical analysis. Due to their complementary utility, a combination of C19Mab-1 (established using CBIS) and C19Mab-3 (established using conventional method) could be useful for the pathological analysis of CD19.

Keywords: CD19; hybridoma production; monoclonal antibody.

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / pharmacology*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Flow Cytometry
  • Humans
  • Immunoglobulins / immunology
  • Lymphocyte Activation / drug effects
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Mice
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antigens, CD19
  • CD19-specific chimeric antigen receptor
  • Immunoglobulins
  • Receptors, Antigen, T-Cell
  • blinatumomab
  • tisagenlecleucel