Monoclonal antibody humanization

CD52 monoclonal antibody, humanized [SY] CAMPATH-1 [TR former reg. to Welcome Foundation]... 

Synonyms Campath-IH DNA-derived Humanized Monoclonal Antibody Humanized IgG I Anti-CD52 Monoclonal Antibody Trade names Campath (Berlex) MabCampath (Schering) Indications B-cell chronic lymphcyotic leukemia, non-Hodgkin s lymphoma... 

Roguska M A, Pedersen J T, Henry A H, et al. (1996). A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing. Protein Eng. 9 895-904. 

The conjugation of monoclonal antibodies (MoAbs) to radioisotopes, chemotherapeutic agents, and protein toxins has also been given consideration (65). Large amounts of human MoAbs can be produced by biotechnological means. 

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

Whereas epidermal growth factor (EGF) enhances the radiosensitivity of human squamous ceU carcinoma cells in vitro (197), addition of EGF to hormone-deprived MCE-7 breast cancer cells prior to irradiation results ia iacreased radioresistance (198). An anti-EGE-receptor monoclonal antibody blocks the abiUty of EGE to enhance growth and radioresistance. Tumor cells, the growth of which is stimulated by EGE, appear to be protected those where growth is iohibited are sensitized (198). 

To date, the most extensively studied polyboron hydride compounds in BNCT research have been the icosahedral mercaptoborane derivatives Na2[B22H22SH] and Na [(B22H22S)2], which have been used in human trials with some, albeit limited, success. New generations of tumor-localizing boronated compounds are being developed. The dose-selectivity problem of BNCT has been approached using boron hydride compounds in combination with a variety of deUvery vehicles including boronated polyclonal and monoclonal antibodies, porphyrins, amino acids, nucleotides, carbohydrates, and hposomes. Boron neutron capture therapy has been the subject of recent reviews (254). 

A higher than expected incidence of CHF is also observed in patients treated with DOX and other cytotoxics (e.g., the taxane paclitaxel) or new generation targeted agents (e.g., the humanized anti-ErbB-2/neu monoclonal antibody trastuzumab) [3]. The cardiotoxic synergism of DOX with taxanes or... 

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

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. 

Humanized Monoclonal Antibodies. Figure 1 Schematic representation of mouse, human, chimeric and... 

Humanized Monoclonal Antibodies. Table 1 Major monoclonal antibodies FDA approved for clinical use... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

Anticytokine receptor antibodies Basiliximab, Da-cluzimab Both are humanized monoclonal antibodies against the IL-2 receptor that block T-cell proliferation by inhibiting IL-2 and thus decrease the T-cell mediated frequency of rejection episodes in organ transplantation. 

Muronomab-CD3 is a murine monoclonal antibody directed against the CD3 complex of the T-lymphocyte antigen receptor. This drug selectively diminishes the T-lymphocyte pool resulting in a strong lymphopenia. Similar to other nonhuman antibodies the generation of human antimurine antibodies (HAMA) limits its long-term use. 

This is a humanized anti-CD52 monoclonal antibody. At present it is in clinical use after bone marrow transplantation and for the treatment of refractory chronic lymphocytic leukemia. 

The chimeric human/murine (basiliximab and dacluzi-mab) or murine (inolimomab) monoclonal antibodies are specifically directed against a part (CD25) of the interleukin-2 (IL-2) receptor. Binding of one of these antibodies to CD25 thereby displaces physiological IL-2 and prevents proliferation of activated T-lymphocytes. 

---