As soon as Köhler and Milstein described hybridoma technology for generating monoclonal antibodies in 1975,1 the biomedical community began working to convert these tailor-made reagents into pharmacological magic bullets. Success didn't take long: In 1986, Orthoclone OKT®-3 from Bridgewater, NJ-based Ortho Biotech became the first therapeutic monoclonal antibody (mAb) to gain Food and Drug Administration approval for use as an immunosuppressant to reverse transplant rejection.
But therapeutic mAbs did not take off as expected because the nonhuman molecules (usually murine), generated using conventional hybridoma technology, do not fare well in human patients. Mouse mAbs have a short serum half-life in humans, limiting their efficacy, and they don't interact optimally with the human effector system, an important component of some treatment scenarios. Perhaps most discouraging: They can actually trigger an immune response. As a result, the once-considerable hoopla surrounding therapeutic mAbs died down for some time.
However, as advances in genetic ...
