New technologies to generate an advanced human monoclonal antibody resource
Wouldn’t it be great to have “magic bullets” of exquisite specificity, to destroy any disease-causing target?
Paul Ehrlich thought that antibodies might be the answer, but how to isolate the right ones from the myriads that human beings can make? Georges Köhler, in his twenties, did just that in mice. Right after his invention of the hybridoma technique, he held a seminar at the Basel Institute for Immunology. At the end of his talk, Niels Jerne, the director of the institute, said: “This is great work; the only downside of it is that you did not do it here.” Shortly after the publication of his paper, Köhler rejoined the Basel Institute. Hoffmann-La Roche, which sponsored the Basel Institute, soon established an enthusiastic monoclonal antibody group under the direction of Ruggero Ceppellini, and later of Theo Staehelin. Monoclonal antibodies took off immediately for use as diagnostics and laboratory reagents of exquisite specificity. Both basic and clinical scientists have been very happy with these tailor-made tools produced from a seemingly inexhaustible cornucopia.
“This is great work; the only downside of it is that you did not do it here.” – Niels Jerne
Although Köhler also conceived of the monoclonal antibodies as therapeutics, the adaptation to this purpose was slow. This was distressing, mainly due to the choice of targets rather than to flaws in the technique or failure to grasp its importance. The technique worked best with mouse cells, but the mouse antibodies are rejected by humans. So, why not make mice produce human antibodies? Pioneer Nils Lonberg and others succeeded in generating such mice in the 1990s, but these mice had a limited (and expensive) antibody repertoire that was difficult for the biotech community to acquire. Over time, recombinant DNA techniques made genetic changes easier and more precise. Mice now had the full human antibody repertoire, but access to them was still out of reach for most companies and clinical scientists. At the same time, targets for antibody attack were being defined for cancer, autoimmune disease, and infectious disease.
If only we had an affordable human antibody mouse! That challenge brought the TRIANNI scientists together and they officially formed the company in 2010. By combining the latest DNA synthesis technology with recombinant DNA technology to “surgically” replace the mouse immunoglobulin exons with human ones, we kept the noncoding control sequences of mouse origin. Our mice make antibodies just like humans—a high-end solution for everyone eager to cure a disease with monoclonal antibodies.