Tuesday, April 10, 2007

Best Hope Vaccine Cures

To understand this blog, you must know that in terms of autoimmune disease the more T-regulatory cells (T-regs) the better. T-regs are an autoimmune patient’s friend. On the other hand, T-effectors are autoimmune “bad guys.” T-eff are busy attacking the patient’s tissues and calling in other nasty immune cells to further damage the tissue.

T-effectors can be converted to T-regs and vice a versa. To get well we want the balance between the two pushed toward the T-reg side. Both are T cells, a kind of white blood cell. They both originate in the bone marrow.

Yesterday this blog was devoted to “allergy shot” autoimmune cures. Those cures try to induce tolerance by injecting tiny amounts of the target of the autoimmune attack into a patient over time. The goal is to increase adaptive T-reg population or to convert T-effectors into T-regs. The more Tregs or Teff that act as Tregs the more tolerance the patient’s immune system would have for the auto-protein under attack in the patient’s body.

It was only two years ago that Arne N. Akbar of the Windeyer Institute of London showed that this conversion was possible in a paper he presented at the Cancer Vaccines 2005 Conference. He showed that T-regs are not fixed in time and made only in the thymus (which completely degenerates by the time you are about 21 years old). Previously researchers had hypothesized that no increase in T reg populations could be created in patients who were too old to still have a thymus.

Dr. Akbar showed that patients older than 21 years can hope to get more T-regs. The “allergy shot” therapy being developed (too slowly) at UCLA is one way to do that. But it is not the only way. Below I describe even more effective vaccines to move the immune balance (homeostasis) toward the T-reg side. The most promising, the closest one to being a cure for all autoimmune diseases, is the one developed using p277 peptide by Dr. Irun Cohen at The Weizmann Institute of Science Immunology Department in Israel. More on that cure at the end of this blog.

You may which to skip the next few paragraphs that describe how autoimmue vaccine cures work and go directly to the highlighted cures at the end.

Following is a description of the four best hopes for vaccine cures for autoimmune disease. Several have been developed for cancer but may easily be applied to autoimmune disease. Both cancer and autoimmune disease share the similarity of out of control reproduction of maladapted cells that the immune system fails to notice and destroy. Many cancer treatments have good efficacy in the treatment of autoimmune disease as well. One example is methotrexate. It started as a cancer treatment, but today it is used for most autoimmune diseases. It stops out of control cell proliferation.

Autoimmune vaccines work in three ways. They can cause the death of the out of control immune cells. They can cause those cells to be converted to harmless or even helpful. (Most vaccines seek to turn up the function of T-regs and convert existing Teffectors into T regs). Thirdly they can stimulate extra production of "good guy" immune cells to turn off the autoimmune response.

In research jargon a T-reg is a CD4+CD25hiFOXP3+ T cell. A T effector is a CD4+CD25-FOXP3- T cell. In the autoimmune “good guy” cells, the CD 25 is up high and FOXP3 is working. In the autoimmune “bad guy cells,” CD25 is off and so is FOXP3.

By turning on CD25 and FOXP3 the very cells attacking your body can be converted from attacking and destroying your tissues into cells that are protecting and guarding those very tissues. This is so cool.

Conversion of T-effectors into T-regs allows for autoimmune remission. It is not an absolute cure. At some point the disease could come back. But it would feel like a cure. A patient could not tell the difference between a T effector conversion and a cure.

Back to the vaccine cures. When you have an autoimmune disease, your immune system
precursors in the bone marrow are producing way too many of a few kind of cells for
example autoimmune B cells. These "bad guy" B cells (aka memory T cells) induce your immune system balance (homostasis) to get out of whack.

These maladapted B cells produce autoantibodies that attack and label your own tissues as "the enemy". Such a large amount of labeled "enemy" cells inside of you causes the T cell population to be pushed toward T effectors and away from T regs.

Another cell that can be out of control is the dendritic cell. It can wrongly activate autoimmune B cells. A third kind of out of control cell can be mast cells which activate dendritic cells which activate autoimmune B cells which make autoantibodies and the autoimune cacade begins.

All three are bone marrow products. All autoimmune disease is bone marrow disease.

The out of control proliferation of B cells, T-eff cells, dendritic or mast cells can be slowed with DMARDS-methotrexate, Plaquenil, Arava, etc. DMARDS target cells that are
reproducing too quickly and cause them to die.

Or a vaccine can be used to get your own immune system to notice that one or two kinds
of cells are reproducing too quickly. This kind of vaccine is even closer to a cure than the allergy shot kind of vaccine of yesterday. This kind of vaccine offers hope for cures for both autoimmune and cancer. Once the immune system is cued to notice the out of control cells, the immune system eliminates them. This kind of vaccine cues the immune system. It stimulates normal immune system auto-correcting processes to function as they are supposed to and stop the autoimmune disease process.

Cure 1: At Stanford Medical Center skin cancer vaccines have been studied for at least the last five years. The brother of one of my college roommates is alive today five years after getting a diagnosis of incurable fatal melanoma. At Stanford he was given injections of treated melanoma cells from other patients with melanoma. His immune system first noticed that the foreign cells and attacked and eliminated the other patient’s melanoma cells. Somehow during the attack on the other patient’s cells, his immune system was cued to also notice melanoma cells. After the foreign melanoma cells were eliminated, his immune system went on to eliminate all of his own melanoma cells spread throughout his body. He is five years cancer free. Are you listening, Elizabeth Edwards?

A very similar therapy has been used at the Weizmann Institute of Science in Israel to cure autoimmune disease. The idea is to get your immune system to notice the autoimmune “bad guy” cells that have way over proliferated. Once the patient’s immune system is cued to notice its own “bad guy” cells, it will eliminate or convert them to harmless or even helpful cells.

Imagine my son with psoriatic arthritis. We find another patient with PsA, perhaps his cousin who also has PsA. Take some of the maladapted autoimmune causing cells from their blood and switch them. Give my son his cousin’s cells and his cousin, my son’s cells. Each of their immune system notices the foreign cells and eliminates them which starts a cascade that then eliminates or converts all their own autoimmune T-effs (or autoimmune causing dendritic cells). The PsA is stopped for both of them. They both walk out without their canes.

Cure 2: At Cedars-Sinai Medical Center in Los Angeles rather than using cells from a different patients, some of a cancer patient’s own healthy cells were taking out, grown and infused with a virus containing IL-23. IL-23 is an immune system signaling molecule (cytokine). The cells that were taken were not cancer cells but dendritic cells. Dendritic cells are supposed to notice out of control cell growth and eliminate it. For some reason, in cancer (and autoimmune)patients the dendritic cells fail to notice the out of control proliferating cells. The I-23 labeling of the dendritic cells allows the cells to "see" better. The dendritic cells suddenly can "see" the out of control cells. The dendritic cells then eliminate them. See "Combined therapies may boost immune response and long-term protection against brain tumors."

Virally altered IL-23 dendritic cell therapy could work for over proliferating immune cells in our bone marrow as well. Our dendritic cells should be noticing the over proliferation of the "bad guy" autoimmune causing cells in our bone marrow and elminating them. Dendritic cell immunotherapy should be tried on the bone marrow of autoimmune patients today not decades from now.

Cure 3: PharmaFrontiers is doing a similar trial with Multiple Sclerosis patients. They are using the patients own cells. This time however they are using T effectors. The researchers are extracting the T-effs from the blood of the patient. Multipling them in the lab. Then irradiating them to slightly damage the cells and finally re-injecting the slightly damaged cells. The patient’s immune system can then “see” these slightly damaged cells. The now cued immune system notices there are way too many T effectors in the blood and command them to change to T-regs. Voila! The autoimmune disease is as good as cured. In a tiny trial of 15 human patients, flare ups were reduced 92%. See “MS vaccine testing to start in the US” BBC News 2006/03/08”

Cure 4--BEST HOPE--The p277 cure: A true cure of all autoimmune cures may have been discovered by Prof. Irun Cohen of the Weizmann Institute of Science Immunology Department. He discovered a way to get any immune system to make more T-regs with a simple vaccination of a protein he discovered. The protein is called HSP60. He recently discovered that even a tiny fragment of it labeled p277 is able to shut down the autoimmune response. Vaccinations with p277 are being used currently in human trials in the United States and Europe for autoimmune diabetes.

Vaccination with p277 converts T-eff to T-regs. It should work for any autoimmune disease. See “The molecular mechanism of a diabetes vaccine revealed.”

Then why is it only being tested on autoimmune diabetes? Well because juvenile diabetes (aka type I or autoimmune diabetes), RA and MS affect many more patients than the other "orphan" autoimmune diseases. The more potential patients, the more potential profit. Therefore the big three autoimmune diseases hog all the best new medicines and therapies.

Sadly current western medicine practices separate autoimmune disease into the 80 different targets of the disease rather than recognizing the unity of autoimmune disease as one bone marrow disease that hits different targets in different patients. All autoimmune disease starts and is sustained by a bone marrow error. Fix the error, fix autoimmune disease.

Autoimmune patients with the most popular (common) diseases always get the good therapies first. That is why we need to push for The Three Musketeer Autoimmune Research and Clinical Testing Rule: One (autoimmune) cure for all. All (autoimmune patients) for that one cure. If we worked together the cures would be here in a year or less.

Cure 5: The last kind of vaccine I call an “Ant Poison” Antigen Cure” for autoimmune. It works like ant bait. In the yard only ants are attracted to the bait. Only ants and their colonies are killed. Other insects ignore the bait and are unharmed. The same principle is used in this kind of autoimmune cure. Only “bad guy” autoimmune causing cells are attracted to the bait. The rest of the immune system is left alone. This type of vaccine in cancer therapy is often called a Trojan Horse vaccine.

This vaccine would very selectively prune out only the autoimmune parts of your immune system. A cellular poison (or radioactive atom) is hooked to the autoimmune antigen under attack by the immune system. The idea is to eliminate only the “bad guy” B cells. The antigen must act as a super antigen that directly interacts with the B cell without dendritic cell presentation of antigen. This half bait (super antigen) and half poison vaccine would kill only the “bad guy” B cells that are producing the autoantibodies.

Without autoantibodies labeling parts of your body as “the enemy” dendritic cells would ignore those body parts that were previously under autoimmune attack, T-effectors would also ignore them, as would macrophages. The body parts (joints, tendons, skin, pigment, muscle, myelin sheath, etc.) would then heal. If T effectors are not simulated to attack, they revert to T regs and protect these tissues not destroy them. The dendritic cells and macrophages wander off to look for real enemies. Your joints, skin or whatever that was being attacked would suddenly get better. Autoimmune disease is over.

How many decades before we get these cures? Do you want to wait? Why not start massive human testing in six weeks for each of these vaccine ‘cures’ in all eighty types of autoimmune disease? Could some people be injured or die? Possibly but aren’t we being injured and dying now? At least we would have a chance for a cure. I would be willing to bet big money that far less patients would be hurt in an aggressive hunt for a cure then are being hurt and dying today from all autoimmune diseases combined.

Get mad. Take action. Demand aggressive human trials. Eliminate exclusion criteria from clinical trials. All for one. One for all! Cures today!

Next planned topics: Trojan Horse Cures, stem cell cures, clinical trials-why really sick patients can not get in, Physician inexcusable ignorance of current research and repulsive condescension to autoimmune patients, problems at the FDA that slow new cures to a crawl, need for a new AMA sanctioned medical specialty licensing for autoimmune and immune dysfunctions.

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