Chimpanzees monoclonal antibodies

Crowe J E, Jr, Cheung P Y, Wallace E F, et al. (1994). Isolation and characterization of a chimpanzee monoclonal antibody to the G glycoprotein of human respiratory syncytial virus. Clin. Diagn. Lab. Immunol. 1 701-706. 

P17. van der Poll, T., Levi, M Van Deventer, S. J., Ten Cate, H., Haagmans, B. L., Biemond, B. J., Buller, H. R Hack, C. E., and Ten Cate, J. W., Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83,446-451 (1994). 

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... 

Anti-CD4 monoclonal antibodies are used to treat various autoimmune diseases, such as rheumatoid arthritis, asthma, and psoriasis (1-3). Keliximab (rINN) (IDEC CE9.1) is a human-cynomolgus monkey chimeric (prima-tized) antibody with specificity for human and chimpanzee CD4. Clenoliximab (rINN) is an immunoglobulin G4 derivative of keliximab. These antibodies induce a more than 80% down-regulation of CD4 molecules on the surface of T lymphocytes. 

Primates may be needed when it becomes clearer that the parameters of interest (hematology, blood chemistry, histopathology, etc.) can only be studied in species that are phylogenetically closer to H. sapiens. This is often the case when candidate drugs are proteins (e.g. animal-derived monoclonal antibodies), and antibody formation may be major issue and may dictate the choice of species. For example, it may be known that only the chimpanzee does not develop neutralizing antibodies to the drug, which would lead one to select that species as the nonclinical model. 

Emini E.A., Schleif W.A., Nunberg J.H. et al. 1992. Prevention of HlV-1 infection in chimpanzees by gpl20 V3 domain-specific monoclonal antibodies. Nature355 728. 

In chimpanzees, administration of Fab fragments of a monoclonal anti-F-VII antibody preceding an endotoxin bolus injection effectively blocked the activation of the coagulation pathway (B25). Administration of monoclonal anti-lL-6 under the same experimental conditions attenuated the activation of coagulation, while the fibrinolytic system remained unaltered. However, administration of monoclonal anti-TNF enhanced the tendency to microvascular thrombosis (P17,18). Monoclonal anti-TF antibodies administered to baboons as a pretreatment attenuated coagulopathy after induction of E. coli sepsis in these animals (T4). Primates pretreated with anti-C5a antibodies before infusion of E. coli developed less hypotension and had better survival rates than untreated animals, who developed ARDS and septic shock with a mortality rate of 75% (S35, Z6). No favorable treatment results have been published yet with one of these treatment modalities given to humans. 

---