What is ch14.18?


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03-11-09 11:02 AM
What is ch14.18?

Chimeric Monoclonal Antibody 14.18 (ch14.18) is an antibody that is part human and part mouse.  It is a chimeric composed of the murine (mouse) monoclonal antibody 14.G2a and human constant region genes.  The 14G2a antibody is a variant of the murine 14.18 IgG3 antibody targeted to the GD2 antigen. 14GD2a was chosen because it had been found to be more potent than other variants.

The 14.18 antibody is separate and distinct from 3F8 yet they are similar murine IgG3 monoclonal antibodies.  The problem with these purely murine antibodies is that they are extremely immunogenic.  In other words, they prompt strong  responses by the immune system because they are foreign to the human body.  This immune response can destroy the antibody before it has the opportunity to target the neuroblastoma cells.  This reaction, called Human Anti-Mouse Antibody (HAMA) response, not only blocks the effectiveness of antibody therapy but also prevents further immunotherapy.   Moreover, HAMA responses may be associated with significant adverse events such as serum sickness and anaphylaxis (extreme allergic reaction).  In order to make these antibodies less immunogenic, prevent HAMA, and reduce these serious side effects scientists have made an effort to replace certain parts of the murine antibody with a human counterpart.  Ch14.18 is the result of this effort.  The ch14.18 is approximately 25% mouse and 75% human and thus less likely to produce a HAMA response or, in this case, a HACA (Human Anti-Chimeric Antibody) response.  In short, ch14.18 is less ?mousy? than its murine antibody counterparts 14.18, 3F8 and 14G2a.