Monoclonal humanized

Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, is reserved for patients with chronic severe asthma inadequately controlled by high-dose inhaled corticosteroid plus long-acting B-agonist combination treatment (eg, fluticasone 500 meg plus salmeterol 50 meg inhaled twice daily). This treatment reduces lymphocytic, eosinophilic bronchial inflammation and effectively reduces the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgE-mediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injections. 

Due to discrimination from species to species, protein A resins can be used to separate monoclonal antibodies from transgenic milk. Autologous antibodies are not adsorbed if the animal is well chosen. For instance, monoclonal humanized IgG expressed in goat milk can be separated. 

Elevated levels of immunoglobulin E (IgE) in the respiratory lumen and blood are associated with allergic asthma. Sweeney et al. measured concentrations of a monoclonal humanized antibody against IgE (E25) in the blood and bronchoalveolar lavage of different animal species and humans following administration into the respiratory tract. Only small quantities of the antibody were absorbed over a period of several days. The authors suggested that the mechanism of uptake was non-specific. ... 

Rabies antibody (LC/HC), monoclonal, human 3pg/gFW(0.07%TSP) Tobacco leaves [9] ... 

Till, M. A., Zolla-Pazner, S., Gorny, M. K., Patton, J. S., Uhr, J. W and Vitetta, E. S. (1989) Human immunodeficiency virus-infected T cells and monocytes are killed by monoclonal human anti-gp41 antibodies coupled to ricin A chain. Proc. Natl. Acad. Sci. USA 86, 1987-1991. 

Vidal MA, Conde FP Alternative mechanism of protein A-immunoglobulin interaction the VH-associated reactivity of a monoclonal human IgM. J Immunol 1985 135 1232-1238. 

Marani E, Tetteroo PAT (1983) A longitudinal band-pattern for the monoclonal human granulocyte antibody B4,3 in the cerebellar external granular layer of the immature rabbit. Histochemistry, 78, 157-161. 

These results contrast markedly with sequence data obtained with monoclonal human or mouse k chains, or with human X chains, where the sequence differences observed between a randomly chosen pair of chains of the same type or subt3q)e are much greater and also involve portions of the V region other than hypervariable segments. 

Fig. 4 20. Carbohydrate structures found in monoclonal human IgG and IgM proteins. Both branched and mannose-rich structures are found in IgE, but only the branched type has been identified in IgA. From Baenziger and Komfeld (139a).

MCC-465 is a pegylated-hposomal doxombicin tagged with a newly developed monoclonal human antibody, named GAH (11,12). At the present, the antigen recognized by GAH antibody is not weU characterized one reason for this is that the western blot analysis with GAH is not applicable probably because the antibody may recognizes the complex conformational integrity of the antigenic epitope. 

Liu J, Lester P, Builder S, Shire SJ. Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE. Biochemistry... 

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. 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

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