Monoclonal chimeric

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

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. 

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... 

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... 

Brouwers, A.H., Buijs, W.C.A.M., Oosterwijk, E., Boerman, O.C., Mala, C., De Mulder, P.H.M., Cortens, F.H.M., and Mulders, P.F.A. (2003) Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with 131-1 or 111-In An intrapatient comparison. Clin. Cancer Res. 9(Suppl.), 3953s-3960s. 

Infliximab (Remicade) is a chimeric monoclonal antibody directed against TNF-a. Recently, its indications have been expanded to include psoriatic arthritis and treatment of adults with chronic severe plaque psoriasis. An advantage over other systemic psoriasis treatments is that infliximab does not adversely affect blood counts, hepatic enzyme levels, or kidney function. The recommended dose is 5 mg/kg as an IV infusion at weeks 0, 2, and 6, then every 8 weeks thereafter. For psoriatic arthritis, it may be used with or without methotrexate. Adverse effects include headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infec-... 

Cetuximab is a chimeric monoclonal antibody directed against epidermal growth factor receptor. Common adverse events include acne-like skin rash, asthenia, lethargy, malaise, and fatigue. 

Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, has become one of the most widely used therapies for follicular lymphoma. Rituximab is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy for patients with stable disease or with partial or complete response following induction chemotherapy. 

Priliximab (cM-T412) is an anti-CD4 chimeric monoclonal antibody that was evaluated in the clinic for the treatment of autoimmune diseases. Priliximab binds to CD4 on the surface of T cells and leads to a profound and sustained decrease in circulating CD4+ T cells decreased counts have been reported to be below normal levels at 18 and 30 months following single- and multiple-infusions.81 Similar findings were observed in preclinical studies in chimpanzees.82 The administration of priliximab was also associated with a cytokine-release syndrome that caused transient fever, myalgia, chills, headache, nausea, and/or hypotension that was accompanied by an increase in serum IL-6. Although evidence of efficacy was observed in clinical trials for CD, the... 

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. 

Moreland, L.W. et al., Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody, Arthritis Rheum., 36 307, 1993. 

Jonker, M. et al., Anti-CD4 treatment with chimeric monoclonal antibody results in prolonged CD4+ cell depression (abstract), J. Cell. Biol., 15E, 179, 1991. 

Reff, M.E. et al., Depletion of B cells in vivo by chimeric mouse human monoclonal antibody to CD20, Blood, 83, 435, 1994. 

Paboiji, M., N.L. Pochopin, W.P. Coppola, and J.B. Bogardus (1994). Chemical and physical stability of chimeric L6, a mouse-human monoclonal antibody. Pharm Res 11(5) 764-771. 

Bonner, J.A. et al., Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck a phase III study of high dose radiation therapy with or without cetuximab, Proc. Am. Soc. Clin. Oncol., 22, 489S, Abstr. 5507, 2004. McLaughlin, R et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma half of patients respond to a four-dose treatment program, /. Clin. Oncol., 16, 2825-2833, 1998. 

Chimeric antibodies can be expressed in mammalian cells by introducing the recombinant DNA that codes for the antibody into the cells and selecting for the rare cell that has integrated the DNA into its own chromosomes and then expresses a new protein — the desired antibody. Additional genetic manipulations of the mammalian cells are then required to select cells that secrete large amounts of the recombinant protein. Following this research and development model would theoretically lead to successful monoclonal therapies, but in practice, it had never been accomplished before the IDEC team developed rituximab. 

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