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Humanized Antibody: Production & Definition

Instructor: Bridgett Payseur

Bridgett has a PhD in microbiology and immunology and teaches college biology.

Lab-made antibodies, produced in mice, are used medically to help treat diseases. Mouse antibodies aren't compatible with human immune systems, so humanized antibodies are produced instead.

Lab-made Antibodies

Have you ever traveled to a foreign country, but didn't know the language? It would be difficult to ask for directions, order food, or get whatever help you happen to need. Having a small dictionary might help, but in the end, you would need some way to translate.

Proteins in your body are very similar. They can't understand foreign things, like mouse proteins, and the mouse proteins can't understand yours. Scientists have been working on ways to help proteins from different species communicate with each other.

Antibody Structure

To understand how and why antibodies need to be humanized, we need to go over some background information. First off, what is an antibody? An antibody is a protein made by special immune cells, called B cells, that help target pathogens to be removed from the body. Antibodies can work by grabbing onto the pathogen and acting as a signal to other cells in the body, saying, ''Come over here and eat this guy!''

Antibodies are shaped like the letter Y. There are two long protein chains that each make up one arm and the body, and two small chains that make up the arms. The long chains are aptly named the heavy chains, and the small chains are the light chains.

The tops of the arms are called the variable region, because this will vary from antibody to antibody. The unique variable region of each antibody binds to one specific antigen, a marker on the bad guys. The rest of the antibody is called the constant region. The constant region is going to be the same on various types of antibodies.

An antibody showing heavy chains in blue and light chains in red.
Antibody

Antibody Functions

An antibody's function is determined by its constant region. Antibodies that have the same constant region and functions are members of the same isotype. Some of these isotypes are made of multiple Y's joined together, like IgM, which is made of 5 Y's. Another isotype can be secreted into the mucosa of the gut and lungs, or into tears, to provide immunity in those locations.

Antibody functions can include opsonization, which is a fancy word for targeting a bacterium to be eaten by immune cells; activating complement, a process that results in a hole being formed in the bacterium to kill it; or starting allergic responses.

Purpose of Humanized Antibody

So, now we know what antibodies look like, and what they do. But why do we need humanized antibodies? And what is a humanized antibody anyway?

Well, as the name implies, a humanized antibody is an antibody that has human components. Antibody from another animal, normally a mouse, has the constant region removed and replaced with a human constant region. This allows the antibody to be used by a human. Human immune systems won't recognize the instructions from a mouse antibody constant region, so you have to change the language so the human body can understand the antibody.

In addition, a human's immune system could see the mouse antibody as ''foreign'' and attack it. This would, of course, make the antibody completely useless therapeutically.

These humanized antibodies can be used in patients to treat autoimmune diseases, cancer, bone loss, and certain infections. They work by activating the immune system to target and attack whatever is causing the patients' disease or symptoms.

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