In Vivo Modeling


Antibodies are ideal tools for In Vivo Modeling of human disease and therapy thereof in experimental animals. In animal models, antibodies are used either to elicit disease such as experimental glomerulonephritis and antibody induced arthritis, or to treat established disease. Specifically, when an accessible molecular target such as a cell surface receptor or a secreted cytokine are suspected to be involved in a disease process, antibody-mediated blocking (neutralization) of this antigen in a disease-relevant animal model can produce the first in vivo proof-of-concept for this hypothesis, motivating full-fledged discovery and development of drugs against this target. In some cases, the proof-of-concept antibody or secondary antibody-leads were developed into therapeutics proper through chimerization and humanization, leading to very successful recombinant antibody medicines such as Remicade™ and Xolair™. Cancer-specific cell-surface antigens are particularly attractive targets for therapeutic antibodies, because independently of any role of the target in cancerogenesis, binding of antibody to the cancer antigen often eliminates the underlying cancer cell in a process known as antigen-dependent cellular cytotoxicity (ADCC). Herceptin™, a widely used antibody therapy for breast cancer, is acting through this mechanism.


Inflamed glomerulus in glomerulonephritis
Antibody Solutions has generated a number of antibodies for in vivo modeling applications. We routinely test for endotoxin and guarantee endotoxin-free preparations.

For example, we have made a monoclonal antibody (AS74-P) against the rat Thy1 antigen which induces glomerulonephritis and proteinuria when injected into Wistar rats. Glomerulonephritis is an autoimmune disease of the kidney in which the kidneys' filters (glomeruli) become inflamed and scarred, and slowly lose their ability to remove wastes and excess water from the blood to make urine. End stage glomerulonephritis necessitates dialysis or kidney transplant. Glomerulonephritis often occurs as a complication of other autoimmune diseases such as diabetes and Lupus. Antibody-induced glomerulonephritis in the rat is a valuable animal model for preclinical testing of novel therapies for this disease.


In an example for validation of an asthma target with an antibody, Rosen et al. (2005) treated asthmatic sheep with an antibody to a proinflammatory endothelial adhesion molecule known as sulfoadhesin. Antibody Solutions generated the first batch of antibody used in this study. The antibody was shown to stain lung endothelium and epithelium in asthmatic but not in normal sheep (right), and treatment of the asthmatic sheep resulted in significant reduction of the early phase and abrigation of the late phase asthmatic response in these animals.

Antibody Solutions offers a wealth of expertise in developing antibodies for in vivo modeling. Please contact us with your specific application needs.


Antibody Solutions
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