Figure 2

Evolution of mAbs linked to the need to decrease their immunogenicity. Different methods to obtain mAbs are depicted. Mouse mAbs, the 'hybridoma' cells derived from the stable fusion of immortalized mouse myeloma cells with lymphocytes from immunized mice, are screened to identify individual clones producing identical antibody to a single antigenic determinant [118]. Chimeric mAbs, the murine constant regions of both heavy and light antibody chains (mCH and mCL), are replaced with human counterparts (hCH1, hCH2, hCH3 and hCL1), leaving intact the murine variable portions (mVH and mVL) [119]. Humanized mAbs, only the CDRs of the murine mAbs (mCDRs) from both the mVH and the mVL, are 'grafted' into a human backbone antibody [120, 121]. Human mAbs, 1)Human memory B-cells isolated from patients are immortalized by Epstein Barr Virus (EBV) and CpG oligodeoxynucleotide, and then screened for specific antibody production [122]. 2) Transgenic mice, obtained by a genetic replacement of the mouse immunoglobulin genes with human counterparts, are used to obtain fully human mAbs by traditional hybridoma technology [123]. 3) Antibody libraries, constructed by in vitro combinatorial assembly of human immunoglobulin variable-region gene (V genes) and cloned to provide the display onto phage surfaces, are subjected to a panning against an antigen in order to select specific clones [124]. The first mAbs of each category approved for clinical use are shown. Palivizumab is the first and, so far, only mAb approved for infectious diseases. The endings used to name the different types of mAbs are also indicated.