Humanized antibody

Humanization can be necessary when the process of developing a specific antibody involves generation in a non-human immune system (such as that in mice).

The humanization process takes advantage of the fact that production of monoclonal antibodies can be accomplished using recombinant DNA to create constructs[3] capable of expression in mammalian cell culture.

The step involving recombinant DNA provides an intervention point that can be readily exploited to alter the protein sequence of the expressed antibody.

Examples of chimeric antibodies approved for human therapy include abciximab (ReoPro), basiliximab (Simulect), cetuximab (Erbitux), infliximab (Remicade) and rituximab (MabThera).

Aside from the CDR segments, the portions of the variable regions that differ from those in humans can be corrected by exchanging the appropriate individual amino acids.

Otelixizumab is an example of a humanized chimera currently in clinical trials for treatment of rheumatoid arthritis and diabetes mellitus.

In the United States, this software was developed, patented, and demonstrated, by Protein Design Labs, Inc. in Mountain View, California, in the 1980s and 1990s.

The hypervariable loops of Campath-1 (that contain its CDRs and thereby impart its ability to bind CD52) were then extracted and inserted into a human antibody framework.

[1] Alemtuzumab is approved for treatment of B-cell chronic lymphocytic leukemia[11] and is currently in clinical trials for a variety of other conditions including multiple sclerosis.

[12] There are technologies that completely avoid the use of mice or other non-human mammals in the process of discovering antibodies for human therapy.

These systems rely on the creation of antibody gene "libraries" which can be wholly derived from human RNA isolated from peripheral blood.