Effective production of a human monoclonal antibody against tetanus toxoid by selection of high productivity clones of a heterohybridoma

A mouse.human-human heterohybridoma, N12-16.63, has been described which produces an anti-tetanus toxoid human monoclonal antibody (MoAb). A clone, N12-16.63.49.19, which produces eight times as much MoAb as that produced by the original cell line, was selected by repeating the recloning and selection twice. Two clones, N12-16.63.49.19.69 and N12-16.63.49.19.127, further selected from this clone produced almost 20 times more than that produced by the original cell line. Though the production of MoAb by these clones gradually decreased with repeating transfers, they still produced a large amount of human MoAb even after 3 months of transfer. Human MoAb (IgM) was isolated from the culture supernatants of the original and high productivity clones and the products were confirmed to be identical. Human MoAb was effectively produced by batch culture on the 20 liter scale or a perfusion culture on the 1 liter scale using these high productivity clones.