Therapeutic utility of Monoclonal antibodies

[Guest guest]

Hello all,

Monoclonal antibody therapy is a form of passive immunotherapy. The combination of a mouse B cell that can recognize a particular antigen and a long-lived mouse myeloma cell makes the hybridoma cell, a kind of perpetual antibody-making factory. Because the antibodies are all identical clones made from a single (mono) hybridoma cell, they are called monoclonal antibodies.

One problem with this is that the human immune system can see these antibodies as foreign and can mount a response against them. In the short term, this can sometimes cause allergic-type reactions. In the long term, it means that the antibodies may only be effective the first time they are given; after that, the body's immune system destroys them before they can be helpful. To tackle this problem replace some parts of these mouse antibody proteins with human parts. Depending on how much of the MAb is human, these are called chimeric or humanized antibodies. Some MAbs are now fully human, which means they are likely to be safer and may be more effective. Newer approach uses fragments of antibodies instead of whole ones, which may make them more effective.

Two types of monoclonal antibodies are used in cancer treatments:

Naked monoclonal antibodies are those without any drug or radioactive material attached to them.

Conjugated monoclonal antibodies are those joined to a chemotherapy drug, radioactive particle, or a toxin (a substance that poisons cells).

Naked Monoclonal Antibodies:

Naked MAbs are the most commonly used MAbs at this time.

Some naked MAbs attach to cancer cells to act as a marker for the body's immune system to destroy them. Antibodies now in use in this group include:

· Rituximab: To treat B cell non-Hodgkin lymphoma and (off label) ITP, MAB against the CD20 antigen, found on B cells.

· Alemtuzumab: To treat B-CLL, MAB against the CD52 antigen, present on both B cells and T cells.

Some naked MAbs attach to the specific antigens, which are functional parts of cancer cells or other cells that help cancer cells grow. Examples of FDA approved MAbs of this type include:

Trastuzumab: antibody against the HER2/neu protein. This protein is present in large numbers on tumor cells in some cancers. When HER2/neu is activated, it helps these cells grow. Trastuzumab stops these proteins from becoming active. It is used to treat breast cancers that have large amounts of this protein.

Cetuximab: Cetuximab is an antibody against the EGFR protein, which is present in high amounts on some tumor cells and helps them grow and divide. Cetuximab blocks the activation of EGFR. It is used to treat some advanced colorectal cancers as well as some head and neck cancers.

Panitumumab: This MAb also targets the EGFR antigen. It is used to treat some cases of advanced colorectal cancer.

Bevacizumab: Bevacizumab targets the VEGF protein, which is normally made by tumor cells to attract new blood vessels to feed their growth. Bevacizumab attaches to VEGF, which blocks it from signaling for new blood vessels to form. This MAb is used along with chemotherapy to treat some colorectal, lung, and breast cancers, and is being studied for use against other cancers.

Conjugated Monoclonal Antibodies:

Conjugated MAbs are joined to drugs, toxins, or radioactive substances. The MAb acts as a homing device, circulating in the body until it finds the target antigen. It then delivers the toxic substance to where it is needed most, which lessens damage to normal cells in other parts of the body.

Conjugated MAbs are also sometimes referred to as "tagged", "labeled" or "loaded" antibodies. They can be divided into groups depending on what they are linked to.

MAbs with radioactive particles attached are referred to as radiolabeled, and this type of therapy is known as radioimmunotherapy (RIT).

· Ibritumomab tiuxetan: is used to treat B cell non-Hodgkin lymphoma

· Tositumomab: is used to treat certain types of non-Hodgkin lymphoma

MAbs with chemotherapy drugs attached are often referred to as chemolabeled.

MAbs attached to toxins are called immunotoxins.

· Gemtuzumab ozogamicin: It contains a toxin called calicheamicin, attached to an antibody against the CD33 antigen treat some people with acute myelogenous leukemia (AML).

Scientists are also studying toxins linked to hormone-like substances called growth factors. But because the growth factor/toxin drugs do not contain antibodies, they are not classified as immunotoxins.

The only growth factor/toxin approved by the FDA thus far is denileukin diftitox (Ontak). It consists of a growth factor (IL-2) + diphtheria toxin, used to treat a rare type of skin lymphoma (cutaneous T cell lymphoma).

Regards,

Dr Smita Mali,

JRII, GMC,

Nagpur.