Monoclonals humanized mouse

CN immunoglobulin G (human-mouse monoclonal c7E3 clone p7E3VHhCy4 Fab fragment antihuman... 

Trastuzumab (Herceptin) -humanized mouse monoclonal antibody directed against HER-2/new receptor -fevers, chills, nausea, vomiting, headache during administration -cardiotoxicity (the FDA has not approved concurrent use with doxorubicin)... 

Immunoglobulin Gl, anti-(human interleukin 2 receptor) (human-mouse monoclonal clone... 

H4 gamwal-chain), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [CAS]... 

Immunoglobulin Gi(human-mouse monoclonal clone 1H4 gamma-chain anti-human antigen Tac), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [SY] Immunoglobulin Gi(human-mouse monoclonal clone 1H4 gamma-chain antihuman interleukin 2 receptor), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [SY]... 

FIGURE 9 Interdependence of ionic strength (I.S.) and pH for the adsorption of humanized mouse monoclonal antibodies on a highly substituted cation exchanger CM HyperD F. Open circles represent the behavior of lgG2 close circles are IgG I. Adsorption essentially occurs when the pH is below 4.7 with ionic strengths close or above physiological buffers (12-25 mS/cm). 

BR96 - Doxorubicin immunoconjugate SON 15. BMS 182248. BR96 - DOX Chimeric human/mouse monoclonal antibody linked to 8 doxorubicin mols. Antibody directed against Lewis-Y antigen. 

L, Palazollo P, Nicaise C, Usakewicz J, Hellstrom KE. Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer. Cancer Immunol Immunother 1993 36 267-273. 

Monoclonal antibodies (mAh) are molecules that recognize and bind a specific foreign substance called an antigen. They are produced from a single clone of B lymphocytes. Conventionally, mouse mAh have been generated for experimental and diagnostic use. Techniques have been developed to humanize mouse mAh to facilitate their therapeutic use in humans. It is also now possible to make mAh which are fully human. 

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

Rituximab is a recombinant mouse/human chimeric monoclonal antibody whose in vitro activity varies with the number of terminal galactose moieties glycosylated to the peptide backbone at residue asparagine 301 [8]. The ability to monitor the levels of each discrete species present would allow the manufacturing process to... 

Siegel, S.A. et al., The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo, Cytokine, 7, 26, 1995. 

Liu, A.Y., Robinson, R.R., Murray, E.D., Jr., Ledbetter, J.A., Hellstrom, L, and Hellstrom, K.E., Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity, ]. Immunol, 139, 3521-3526,1987. 

If the antigen of interest is abundant and additional sensitivity is not required, then a two-step direct method, rather than a three-step indirect method, can be anployed. With the two-step method, the primary antibody is a biotin-labeled mouse monoclonal antibody, which is followed directly by the ABC incubation step. Because of the abundance of human immunoglobulins in tissue sections, methods for staining immunoglobulin often employ biotin-labeled mouse antihuman immunoglobulin reagents. 

Basiliximab is a mouse/human chimeric monoclonal antibody with specificity and high affinity for the a-subunit of the IL-2 receptor. The antibody acts as an lL-2Ra antagonist and inhibits lL-2-mediated activation and proliferation of T l)unphocytes. It is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents like cyclosporin, azathioprine, mycophenolate mofetU... 

---