Monoclonal antibodies types

Monoclonal antibodies are produced by hybrid cells created from B lymphocytes fused with immortal B lymphocyte tumor cells. The resulting hybrids can be individually cloned, and each clone will produce antibodies directed against a single antigen type. Two new monoclonal antibody types have been created that are useful in the treatment of cancer. 

A critical step in radioprotection involves the IL-1 receptors. Monoclonal antibodies to the type 1 IL-1 receptor block IL-l-induced radioprotection (167). Although this receptor is not present on BM cells, it is present on fibroblasts, which suggests that the effects of IL-1 on stem cells maybe largely indirect and mediated by stromal cell activation (168). Anti-IL-1 receptor (type 1) also sensitizes normal mice to the effects of TBI, which suggests that endogenous IL-1 has an intrinsic radioprotective role. IL-6 induction by IL-1, but not CSF levels, is inhibited, which supports the concept that G-CSF and GM-CSF are insufficient by themselves at radioprotecting stem cells and indicates a contributory role for IL-6. Anti-IL-6 antibody blocks IL-1 and TNF-induced radioprotection and also decreases the intrinsic radioresistance of mice, as does anti-TNF- a (169). 

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. 

A B lymphocyte is a specific type of white blood cell (leucocyte) derived from bone marrow stem cells. Each B lymphocyte expresses an immunoglobulin (antibody) specific for a particular antigen. Following antigenic stimulation, a B lymphocyte may differentiate and multiply into plasma cells that secrete large quantities of monoclonal antibody. 

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]. 

Kuritzkes DR, Jacobson J, Powderly WG, Godofsky E, DeJesus E, Haas F, Reimann KA, Larson JL, Yarbough PO, Curt V, Shanahan WR Jr (2004) Anthetroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1. J Infect Dis 189 286-291... 

In addition to the three types of immunological product that are generally available there are two further types synthetic peptide vaccines and monoclonal antibodies. Both have been extensively investigated but neither has, as yet, a place in conventional prophylaxis or therapeutics. 

Information about the putative folding of the H,K-ATPase catalytic subunit through the membrane has been obtained by the combined use of hydropathy analysis according to the criteria of Kyte and Doolittle [51], identification of sites sensitive to chemical modification [46,48,50,52-55], and localization of epitopes of monoclonal antibodies [56]. The model of the H,K-ATPase catalytic subunit (Fig. 1) which has emerged from these studies shows ten transmembrane segments and contains cytosolic N- and C-termini [53]. This secondary structure of the catalytic subunit is probably a common feature of the catalytic subunits of P-type ATPases, since evidence supporting a ten a-helical model with cytosolic N- and C-termini has also been published recently for both Ca-ATPase of the sarcoplasmic reticulum and Na,K-ATPase [57-59]. 

The most promising types of biologic response modifiers are monoclonal antibodies, cytokines, and fusion proteins.1 Monoclonal antibodies may be chimeric (fused mouse and human segments designated -ximab ), humanized with intermittent murine sequences (designated -zumab ), human backbone with monkey sequences, or fully human.40... 

All monoclonal antibodies end in the suffix -mab. The syllable before -mab indicates the source of the monoclonal antibody (see Table 85-4). When administering an antibody for the first time, one should consider the source. The less humanized an antibody, the greater is the chance for the patient to have an allergic-type reaction to the antibody. The more humanized the antibody, the lower is the risk of a reaction. The severity of the reactions may range from fever and chills to life-threatening allergic reactions (which have resulted in death). Premedication with acetaminophen and diphenhydramine is common before the first dose of any antibody. If a severe reaction occurs, the infusion should be stopped and the patient treated with antihistamines, corticosteroids, or other supportive measures. 

Xiang SH, Doka N, Choudhary RK, Sodroski J, Robinson JE. Characterization of CD4-induced epitopes on the HIV type 1 gpl20 envelope glycoprotein recognized by neutralizing human monoclonal antibodies. AIDS Res Hum Retroviruses 2002 18(16) 1207—1217. 

The limitations of ELISA methods include the specificity of antibodies, the concentrations of primary antibody and antigen, and the type of reaction solution. Nonspecific binding of either of the antibodies to related antigens, unrelated proteins of other bacteria, or even the microtiter plate may lead to false positive reactions.49,52 57 Use of a monoclonal antibody may decrease crossreactivity with other antigens. For detection of low numbers of bacteria, as in drinking water, the sample may be filtered to concentrate the cells or cultured in a selective broth until it reaches the minimum detection limit for ELISA.49,58 Commercial test kits using dipsticks, immunoblots, and sandwich ELISA methods have been developed for the identification of pathogenic bacteria.58,59... 

Parasitism by T. spiralis has been a subject of scientific interest for over 150 years. Recently, considerable attention has been paid to the parasite by immunologists interested in immunity to nematodes in general, and mucosal immunity in particular. It has been shown that glycan-specific antibodies are highly effective mediators of host defence against intestinal 7. spiralis infection. Protective monoclonal antibodies have been used to elucidate mechanisms of worm expulsion, as well as to identify molecules that the parasite uses to create its niche. In the future, detailed characterization of these molecules and their functions should afford additional insights into parasitism by Trichinella spiralis, and possibly also by other types of pathogen. 

TES-32 is the most abundant single protein product secreted by the parasite. It is also heavily labelled by surface iodination of live larvae (Maizels et al., 1984, 1987), and is known by monoclonal antibody reactivity to be expressed in the cuticular matrix of the larval parasite (Page et al, 1992a). TES-32 was cloned by matching peptide sequence derived from gel-purified protein to an expressed sequence tag (EST) dataset of randomly selected clones from a larval cDNA library (Loukas et al., 1999). Because of the high level of expression of TES-32 mRNA, clones encoding this protein were repeatedly sequenced and deposited in the dataset (Tetteh et al., 1999). Full sequence determination showed a major domain with similarity to mammalian C-type (calcium-dependent) lectins (C-TLs), together with shorter N-terminal tracts rich in cysteine and threonine residues. Native TES-32 was then shown to bind to immobilized monosaccharides in a calcium-dependent manner (Loukas et al., 1999). 

The in vivo manipulation of specific type 2 cytokines using anticytokine monoclonal antibodies, or mouse strains with targeted deletions in cytokine and/or cytokine receptor genes, has proved a fruitful approach in identifying the importance of individual cytokines and the responses that they control in contributing to host resistance. These studies have identified important roles for IL-4, IL-9 and IL-13 in host protection against nematode infection, though the relative importance of each cytokine appears to be nematode-species dependent. 

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