Antibody, chimeric

Chimeric Antibodies The first generation is the chimeric antibodies (chimeric comes from the word Chimera, a Greek mythology beast made of three animals a lion, a snake, and a goat). This type of antibody consists of both murine and human parts. The murine Fv fragments are retained and linked to the Fc fragment of human IgG. An example of the chimeric antibody is ReoPro, which prevents blood clots by binding to a receptor on platelets. 

Recombinant technologies enable us to produce bispecific antibodies, chimeric antibodies, and antibody fragments. 

Fig. 3.11. Production of chimeric antibodies. Chimeric genes or cDNA for the heavy and light chains may be assembled into two separate vectors as shown, or may be assembled into a single vector.

Immunomodulatory, Immunosuppresants. TNF-alpha binding antibody. Chimeric Ab composed of human constant and murine variable regions. Produced by a recombinant cell line cultured by continuous perfusion... 

Figure 4 Illustration of chimeric and humanized antibodies. Chimeric antibodies consist of variable regions of a mouse antibody linked to constant regions of a human IgG molecule, whereas humanized antibodies are almost entirely human except for murine CDRs.

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

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

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). 

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. 

Cetuximab (Erbitux) Chimeric antibody, IgGi EGFR Ligand competition ADCC CRC SSCHN... 

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... 

Masiero S, Del Vecchio C, Gavioh R, Mattiuzzo G, Cusi MG, Micheli L, Gennari F, Siccardi A, Marasco WA, Palu G, Parolin C (2005) T-cell engineering by a chimeric T-ceU receptor with antibody-type specificity for the HlV-1 gpl20. Gene Ther 12 299-310... 

Basiliximab and daclizumab are considered monoclonal antibodies. Daclizumab is a humanized antibody that is approximately 10% murine and 90% human, whereas basiliximab is a chimeric antibody that is approximately 30% murine and 70% human.9,11 These agents bind with high affinity to the IL-2 receptor, where they act as CD25 receptor antagonists. These receptors are present on almost all activated T cells. Their role in induction therapy involves inhibiting IL-2-mediated activation of lymphocytes, which is an important step for the clonal expansion of T cells. 

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... 

McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma Half of patients respond to a four dose treatment program. J Clin Oncol 1998 16 2825-2833. 

Rituximab (Rituxan ) Rituximab is a chimeric monoclonal antibody directed against the CD20 molecule on B lymphocytes.21 Similar to other B-cell malignancies, CLL... 

Niwa R, Shoji-Hosaka E, Sakurada M, et al. Defucosylated chimeric anti-CC chemokine receptor 4 IgGl with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res 2004 64 2127-2133. 

J. Newman, J. Albert, D. Anderson, K. Carner, C. Heard, F. Norton, R. Raab, M. Reff, S. Shuey, and N. Hanna, Primatization of recombinant antibodies for immunotherapy of human diseases A macaque/human chimeric antibody against human CD4, Biotechnology, 10, 1455 (1992). 

S. P. Duddu, and P. R. Dal Monte, Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic antibody, Pharm. Res., 14(5), 591 (1997). 

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