Question

a. How does one make a humanized antibody? What are the benefits of humanizing an antibody?

b. Why might there be side effects when an antibody binds to its epitope?

Answer 1

( a) Huminized antibody is a type of antibody which is made in the laboratory by combining a human antibody with a small part of an experimental animal ( usually mouse or rat ) monoclonal antibody. The mouse part of the monoclonal antibody combines with the target antigen and the human part makes it less likely to be destroyed by the body's immune system.

Mice are widely used in laboratory for production of antibodies against a wide range of antigens. The process of Huminization is usually applied to monoclonal antibodies from mice developed for adminstration in humans who need therapeutic care in case of anti cancer drugs.The protein sequences in the antibody is produced in such a way that they are partially distinct from homologous antibodies occuring naturally in humans and hence they become part of immune system in humans . This approach allows optimal humoral response . This high affinity antibodies resulting from this procedure is further characterised and produced as monoclonals . These stratergies are used and the antibodies combined with mice are genetically engineered or engrafted with human immune system.

Also, huminization is done by the process of recombinant DNA technology wherein the production of monoclonal antibodies is accomplished by recombinant DNA which is able to express in cell culture of humans. Here the segments of gene is taken which are capable of producing antibodies and is cloned into the cells which can be grown in bioreactor and the DNA of the cloned genes is harvested for the antibody proteins produced.

Benefits of huminizing an antibody :

Huminizing antibodies is useful in diagnostic and therapeutic applications in medical field.

The first therapeutic use of this huminizing antibodies was done in 1986 for treatment of kidney transplant rejection.

This technique is used to develop drugs which prevents organ transplant rejection.

(b) The antibodies developed by this huminization technique finds its way in treatment purposes. However, as an exogenous protein, these antibodies can be detected by human immune system and in response to it there might be serious side effects. The antibodies binds to different class of its target antigens through this epitope regions. Therapeutic antibodies which are engineered through this huminizing technique has to maintain its specificity and biological function of original antibodies. However, the antibody drug effect is reduced and there might be serious side effects like auto immune disease. Therefore, several methods are considered to detect the epitope region of antibodies to avoid these side effects.