A strategy of targeting B10 cell by CD19scFv-IL10R for tumor therapy

Biochem Biophys Res Commun. 2018 Dec 2;506(4):990-996. doi: 10.1016/j.bbrc.2018.10.191. Epub 2018 Nov 4.

Abstract

IL-10 producing B (B10) cells, a subset of regulatory B (Breg) cells, produce IL-10 and play immunosuppressive roles in antitumor immunity. B10 cells are associated with enhanced tumor-aggressiveness and a poorer prognosis. To specifically inhibit the IL-10 secreted by B cells, we constructed the recombinant plasmid pcCD19scFv-IL10R, which contained the gene of anti-CD19 single-chain variable fragment (CD19scFv) and the extracellular domain of IL-10R1. Soluble CD19scFv-IL10R protein was identified in vitro and in vivo after the cells were transfected with pcCD19scFv-IL10R plasmid or the mice were injected with the plasmid. The fusion protein had the bispecific ability to target both IL-10 and CD19 molecules in vitro. Intramuscularly (i.m.) injecting mice with pcCD19scFv-IL-10R plasmid inhibited hepatocellular carcinoma growth in vivo. Mice treated with pcCD19scFv-IL-10R showed a significant reduction in B10 cells and regulatory T (Treg) cells, but an increase in the anti-tumor Th1 immune response and the cytotoxic CD8+ T cell response. Thus, targeting B10 cells by CD19scFv-IL10R molecule may offer a new avenue for tumor therapy.

Keywords: B10 cell; CD19scFv; IL-10; Tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes, Regulatory / immunology*
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Immunity
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Plasmids / metabolism
  • Protein Binding
  • Receptors, Interleukin-10 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Serum / metabolism
  • Single-Chain Antibodies / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antigens, CD19
  • Receptors, Interleukin-10
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies