Humanized Monoclonal Antibody Therapies in Neoplastic Disease

In the last ten years the treatment of many types of cancer has been revolutionized by monoclonal antibody therapies. There are many, many print and audiovisual advertisements for these drugs bringing them into the public mainstream.. So, this brings to point some important questions: 1) What are monoclonal antibodies? 2) What types of cancer are treatable by this therapy? 3) What is the basic mechanism of action, i.e., How do these drugs work?

Antibodies are the body’s natural immune defense against invading pathogens. They are produced by specific cells of the immune system termed B cells. When an infection of the body occurs, the immune system takes note. After a brief time, when the front line defenses of the immune system battle the infection, [termed the innate immune response- the first line of battle], the cellular part of the fight takes over [the adaptive response]. The adaptive immune response involves antigen presenting cells, T and B cells. Very briefly, what happens within your body when an infection occurs is this: Circulating “detectives” called macrophages and dendritic cells find the infection and literally eat it or eat cells infected [in the case of a viral infection]. The cells then “present” specific protein parts of the eaten pathogen [bacteria or virus–called antigens] to cells called T and B cells. This is a call to arms: this is literally a scream saying “time to kick butt” by the immune system. The T cells are activated by the B cells upon finding the presenting antigen. The B cells then decide that they can better fight by changing themselves into a plasma cell. This is where the action happens. The B cell changes into a protein pumping machine, the protein being antibodies. The antibodies then go find from the blood the pathogen that the original antigen presenting cells early in the infection encountered. When the antibodies find their target, they bind to it and mark it for death. Think of this as a ball with toilet plungers attached. The wooden handle is what tells the immune system, “this thing needs to die”.

This is the basic theory behind monoclonal cancer therapy. Except in the context of monoclonal antibody cancer treatment, the antibodies are produced to a single epitope (a particular protein that the immune system readily sees from a cancer cell). These cells are then taken into the laboratory, grown and stimulated to produce a single antibody that “sees” a cancer cell.

An example of monoclonal antibody treatment in cancer is Herceptin. Herceptin is a monoclonal antibody specific for an antigen called HER2. HER2 is a protein that is more prevalent on cancer cells of the breast than in normal cells. This protein is from a family of receptors that tells normal cells to grow. The drug then takes advantage of this and can specifically target cancer cells of the breast in order to kill them. This drug too has side effects of being NOT heart friendly.

Another good example of neoplastic cancer therapy is the drug termed Rituxan (Rituximab). Rituxan is a monoclonal antibody directed towards the antigen CD20 on circulating lymphocytes of the blood and is indicated for the treatment of non-Hodgkin’s lymphoma. It works by depleting the blood of cells that have over-produced cells that have CD20 on their cell surface. When the antibody binds, like Herceptin, the body sees those cells as foreign and kills them.

So, the question is now that we know what neoplastic antibody therapy is, how does this killing work?
The current research and thinking is that when cancer cells are coated by these antibody drugs, the extending end of the antibody [called the Fc portion] attracts Natural Killer, NK, cells from the immune system. These cells actually have receptors that recognize this very event. When NK cells find antibody coated cells, they bind to them tightly and commence to kill them. The close proximity of the two cells allows the NK cell to release protein degradating enzymes, and other cytotoxic elements to kill the target.
This entire process is termed Antibody Dependent Cellular Toxicity, ADCC.

ADCC is a powerful tool being utilized by numerous biotech companies with the intent to augment the immune response with other, novel drugs. Such drugs that come to mind are TLR agonists, chemotherapy drugs and gene transfer strategies.

Genentech makes Herceptin, while Rituximab is in combination with Biogen Idec/Genentech. Both drugs are multimillion dollar assets to both companies. The side effects of Herceptin have been documented and are under intense research to understand them. Rituxan continues to be a key element to the bottom line of both companies with it’s successful treatments.

Herceptin is produced by Genentech.
Rituxan is another monoclonal antibody treatment indicated for the treatment of lymphoma.

Prostate Cancer Antibody – Promising Treatment For Your Cancer

A number of researchers have revealed an antibody which will bond with prostate cancer tissue and instigate direct cell death while injected into mice. The discovery would nearly be a treatment to cancer of prostate if outcomes carry over to humans.

It is one of the principal diseases frightening men nowadays. The cancer is #2 on the listing of most widespread cancers in men. More than the past 150 years lots of various treatments have been developed as part of research for prostate cancer treatment.

The study published in PNAS {the Proceedings of the National Academy of Science} stated that the antibody, called F77, was discovered to bond more readily with tissues and cells of cancerous prostate than with benign tissue and cells, and to help the death of cancerous tissue.

Even so, the study showed that it did not be intended for normal tissue or tumor tissues in other areas of the body including the colon, kidney, pancreas, skin cervix, lung, or bladder.

Researchers wrote the antibody “proves promising potential for diagnosis and treatment of the cancer, particularly for androgen-independent metastatic prostate cancer,” which frequently extends to the bones and is not easy to treat.

Antibodies are also already being employed to deal with diseases like lymphoma and breast cancer. It is said that until now there has been no successful antibody therapy for cancer of prostate. However, any research team has produced an antibody named F77 which looks so potential. In spite of the research being at a very early step, it brings up the hope of an effectual treatment for advanced prostate cancer.

Paternal Leukocyte Immunization As Therapy for Excessive Sperm Antibodies

There are various factors preventing couples to have children, one of them is because excessive sperm antibodies of the wife. For these cases, PLI (Paternal Leukocyte Immunization) therapy could be an option to quickly have a baby.

PLI (Paternal Leukocyte Immunization) or also known as Husband Leukocyte Immunization Husband (HLI) is treatment to lower sperm antibodies in women who have excessive number of these antibodies.

Excessive sperm antibodies makes it difficult for sperm to get to the egg because it is always rejected and become dysfunctional, so it does not allow for fertilization and pregnancy. Every woman who has been exposed to sperm does have antibodies against the sperm of her husband, but in some women these antibodies overreact.

The cause is the same with people who are allergic, each person has a different response, depending on the individual. Women with high sperm antibodies overreact to proteins on the sperm, so sperm is rejected and become dysfunctional.

PLI therapy is given by injecting husband’s white blood cells to area under the skin of the wife. It aims to reduce the wife sperm antibodies that can be tolerated by the body and allow for fertilization.

The injection is given at least 3 times, each is given every 3 weeks. Serum containing husband’s white blood cells will be injected at the bottom of the mother’s skin. After therapy, patients are advised to do a reassessment of imuno-andrology test. If the result has reached the normal limit then it is not necessary to continue the treatment. If not, repeated therapy can be performed to achieve normal limits.

There are several requirements that must be considered by married couples to be able to perform PLI therapy:

  1. Excessive wife sperm antibodies
  2. Husband is in good health, i.e. a blood test showed that the husband is free from infectious diseases such as HIV, hepatitis and others.
  3. For the wife who has any history of allergy (e.g. seafood allergy), at the time of therapy, the allergy is not in relapsed condition. If therapy is being performed at the time of allergy it can cause an overreaction.

The chance of success in reduction of antibodies can be up to 95 percent, but for the chance of pregnancy depends on the condition of the body, respectively. Difficulty to get pregnant depends on many factors. If it is indeed because of high antibodies then there is high probability you can get pregnant after reduction of these antibodies.

Before PLI therapy was invented, there are 2 ways which are usually conducted to help pair with this problem to get pregnant, that is with the use of condoms and imunosupressor drug.

Women are expected to gradually lower her sperm antibodies by limiting the exposure to sperm by the use of condoms. However, this should take a long time, about 6 months to 1 year. This will be even longer if the wife often eat foods that contain protein allergens.

Another way is to use the imunosupressor drug. Unfortunately, by using this drug all the antibodies in the women’s body will also goes down, not only sperm antibodies. As a result, the wife will often experience illness, and even affect the spinal cord that causes slow blood rejuvenation, lead to osteoporosis, the risk of diabetes, and others.

It is later found that the husband’s white blood cell immunization can lower sperm antibodies exclusively, and keep the other antibodies which are needed. PLI makes good tolerance to sperm.

The wife who has this problem will also have difficulty in getting good result in IVF. This is because the antibodies will not only reject the sperm, but also reject the fetus resulted from fertilization of the sperm. Even if IVF yields successful conception, the percentage of miscarriage is still high. This is because the wife body remained resistant to the fetus.

Women with a history of this problem in the family had a greater risk of experiencing the same thing. A history of certain food or condition allergies also increases the risk of women having excessive sperm antibodies.

About Antibodies for Cancer Prevention

The latest discoveries in medical technology are using certain antibodies for cancer prevention. These medical miracles are called monoclonal antibodies, or “Mabs”, and can be used to help ward off all kinds of cancers. The technology to aid doctors and nurses fight cancer has only come about within the last several decades. Further research continually turns up more and more Mabs, providing hope for those who have already developed cancer and for those who are trying to protect themselves from it.

The American Cancer Society’s (AMC) web site explains that monoclonal antibodies were first developed in laboratories using mice with myeloma cells, which is a kind of bone marrow cancer, and mice that produced specific antibodies for those cells. The combination of these two cells, called a hybridoma cell, forces a perpetual factory making antibodies. The antibodies end up being identical clones of the original hybridoma cell, which is why they are called monoclonal antibodies. The problem scientists faced with this phenomenal finding was that human antibodies recognized the mouse-produced antibodies as foreign invaders and attacked them. With hard work and dedication, scientists are continuing to develop ways to integrate human antibodies in lieu of mouse antibodies so cancer patients will be able to use the immunotherapy as a form of treatment.

Today there are two types of Mabs, naked and conjugated. The difference between these two lies in the fact that naked antibodies lack radioactive materials attached to them. Conjugated antibodies, on the other hand, are fused with a chemotherapy drug or other toxin used to fight off cancer cells. In recent years the Food and Drug Administration (FDA) has approved several Mabs, both naked and conjugated, for cancer treatments. A list of approved Mabs is available through the ACA’s web site. In 2004 and in 2006, Bevacizumab, a naked antibody, was approved for treating certain types of breast cancers. In 2001 the FDA approved the use of Alemuzumab, a naked antibody, which acts as a form of leukemia prevention by attaching itself to both B and T cancer cells, causing the body’s immune system to attack and kill them. In 2000, the FDA approved the use of a conjugated antibody, Gemtuzumab ozogamicin, which is used in the treatment of chronic leukemia.

If you have lost someone to cancer or know someone suffering from cancer, it is not hard to understand how crucial medical research is when it comes to finding antibodies for cancer prevention. The number of cancer victims continues to rise each year, hitting people of all ages. With the prolonged use and approval of Mabs, these numbers may begin to decline, alleviating the fear everyone has about developing some form of the deadly disease. Diet and exercise will only help an individual a certain amount, leaving genetics and medical breakthroughs to do the rest. By continuing to fine tune more variations of antibodies for cancer prevention, medicine as we know it today could be changed for the better in years to come.

Medicine has come a long way in the last fifty years thanks to the help of scientists and research laboratories. Their combined efforts have aided individuals all over the world prevent and treat life-threatening forms of cancer. Advancements in immunotherapy treatments that use antibodies for cancer prevention, combined with other cancer-deterring methods, are just a step on the threshold for greater triumphs to help everyone live long and healthy lives.