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

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.