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Old 11-21-2006, 10:51 PM
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Default Getting the Facts on Lymphoma vaccines - Lymphoma Research Foundation

Getting a vaccine "shot" is the best way to prevent infections like tetanus, polio, and measles. These vaccine shots stimulate your immune system (antibodies and T cells) to fight off the germs that cause these diseases.

New kinds of experimental vaccines are now being studied as treatments for non-Hodgkin's lymphoma (NHL). These vaccines are not designed to prevent lymphoma, but rather treat it once it has arisen, and are thus termed "therapeutic vaccines." As with other types of so-called immunotherapy (e.g., therapeutic monoclonal antibodies), lymphoma vaccines are designed to work by harnessing the power of a patient's own immune system to fight off his or her tumor.

Early clinical trials have demonstrated that tailor-made lymphoma vaccines can result in anti-tumor immune responses which may result in improved survival, elimination of residual disease, and shrinkage of tumors. Several different lymphoma vaccine clinical trials are underway to determine whether lymphoma vaccines are effective. Here are some questions and answers about this new type of therapy for lymphoma.

Q: What are the different types of lymphoma vaccines?

A: Lymphoma vaccines are a form of immunotherapy designed to use a patient's immune system to provide a generalized, long-lasting attack against their lymphoma. All available lymphoma vaccines are custom-made from each patient's tumor cells.

Researchers are evaluating several different lymphoma vaccines: ldiotype vaccines target a lymphoma "fingerprint" called an idiotype, which is a unique portion of an antibody present only on patient's lymphoma cells. This is most common type of lymphoma vaccine (See Table the 1 for listing of ongoing trials). Dendritic cell vaccines are made by mixing, or "pulsing," specialized immune cells called dendritic cells with a sample of a patient's tumor (either idiotype protein or killed lymphoma cells). Dendritic cells are derived from a patient's own blood using special laboratory procedures. Tumor cell vaccines consist of pieces of a tumor (either whole, broken apart and/or combined with an immune stimulant) that are injected directly into a patient. Heat shock protein vaccines consist of proteins purified from tumor cells that have been broken open to release these general immune stimulants.

Q: How are therapeutic lymphoma vaccines different from therapeutic monoclonal antibodies?

A: Monoclonal antibodies (e.g., Rituxan) attack only a single target on the surface of tumor cells, whereas lymphoma vaccines are designed to recruit the entire immune system (antibodies and T cells) to attack the tumor continuously on several fronts. Researchers are hoping that vaccines will offer life-long control for lymphoma, but this has not been proven definitively yet in large-scale trials.

Q: How are lymphoma vaccines made?

A: Scientists use different laboratory techniques to produce the various types of therapeutic lymphoma vaccines. In the case of custom-made idiotype vaccines, either a surgical or needle biopsy is the first step. Researchers create idiotype vaccines by combining the idiotype protein from each individual patient's tumor with a molecule called keyhole limpet hemocyanin (KLH) that the immune system perceives as foreign; this puts the immune system on high alert. In general, idiotype lymphoma vaccines require several months to manufacture, although scientists are testing methods to speed this process. Using modern molecular biology techniques, these vaccines can now be mass-produced in the laboratory. Once the vaccine is made, it can only be used in the patient whose tumor was used to make it. If the vaccine is used up, then more can be made for that patient.

Q: What's involved in getting a lymphoma vaccine?

A: Each lymphoma vaccine trial has specific entry criteria, and you should discuss with your doctor whether you might be eligible to participate in one of these clinical trials. Some trials require that you have never been treated for lymphoma in the past. Others do not have this requirement. At present, the most advanced-stage testing of lymphoma vaccines is being done with idiotype vaccines. In preparation for receiving an idiotype vaccine, you must first have a biopsy to retrieve tumor material to prepare a vaccine that has been tailored to attack your tumor. Two large-scale, randomized (Phase 111) clinical studies are underway to evaluate whether idiotype vaccines are effective in preventing relapse (regrowth) of lymphoma after chemotherapy. Patients who have never had chemotherapy or Rituxan must first have a biopsy, then undergo 6 to 8 cycles of chemotherapy to reduce the number of lymphoma cells in the body. To date, researchers believe that patients have the best chance to respond to a vaccine when they have a low "tumor burden," meaning only a small number of lymphoma cells are present in the body.

Q: How long will the vaccine treatments last?

A: Depending on the trial, the treatment period may last anywhere from 3 to 24 months, during which time you will receive injections every month or so. For example, in the case of one idiotype vaccine trial, each month you will receive two types of injections as part of the treatment process. The first type of injection is the vaccine itself. The second type of injection is something designed to boost your immune system even more. An injection of this second substance, called Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), helps your immune system recruit white blood cells to help the vaccine attack its target (the idiotype molecule on your lymphoma cells). Your doctor must give the first injection of both the idiotype vaccine and the general immune stimulant in a health care facility. After that, your doctor may permit you or a friend or family member to give subsequent shots of the GM-CSF for 3 days at home. Keep in mind, however that each vaccine trial has distinct injection schedules and different rules, so check with your doctor about the specific requirements of the different trials.

Q: Will the injections hurt or cause any side effects?

A: To date, nearly all patients experience some skin redness and tissue swelling at their injection site which lasts 3-7 days. Roughly half of the people who have received experimental vaccine treatment also report symptoms akin to getting the flu, such as mild fevers, aches and pains in the muscles and joints, tiredness, nausea, and headaches. These side effects generally only last a few days and can be treated fairly effectively with over-the counter pain medicines such as aspirin or acetaminophen.

Q: Is vaccine therapy for me?

A: Maybe. Speak to your doctor about whether you may be eligible to participate in a lymphoma vaccine trial. He or she will help you weigh the benefits and risks based upon your medical history, what type of NHL you have, as well as whether you have received prior treatment for your lymphoma. Your doctor may also factor in the results of blood tests and your overall disease prognosis as determined by the NHL International Prognostic Index, a predictive tool researchers have developed to guide healthcare professionals in treating NHL.

Q: Do vaccines work? Are they better than current NHL treatments?

A: Since at present all cancer vaccines are still considered experimental treatments, the jury is still out. To know for sure, researchers must carefully analyze the results of randomized, large-scale clinical trials. Two such Phase III trials of idiotype vaccines are currently under way, and several smaller trials of other vaccine types are also in process. Early results of idiotype trials are promising; most patients treated with an idiotype vaccine show an immune response as determined by blood tests. However, researchers do not yet know whether vaccine therapy will be effective in improving current treatments for lymphoma. At the least, the hope is that vaccine therapy, like antibody therapy, will be less toxic than traditional therapies such as chemotherapy and radiation. Scientists are working hard to assess whether vaccine therapy can help patients with NHL. By participating in a vaccine trial, you can help researchers determine whether vaccines are effective in treating different types of lymphoma (e.g., indolent, aggressive, mantle cell).

Last edited by gdpawel : 02-03-2013 at 06:46 PM. Reason: posted full article
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Old 05-20-2013, 01:52 PM
gdpawel gdpawel is offline
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,360
Default Tumor cell escape from immune attack

Tumor cell evolution enables cancer cells to evade destruction by the immune system. Cells that can be destroyed are destroyed. What is left is resistant to immune destruction. The mechanisms of escape are extremely diverse.

Tumor cells can lose the antigens (a molecule that the immune system reacts against and attacks) that trigger an immune response. In addition, tumor cells can inhibit the immune response, or develop resistance to the killing mechanisms involved.

For a tumor to grow and cause disease in the first place, it must evade destruction bv the immune system. The immune response is therefore a major selective pressure that directs the flow of tumor cell evolution.

This is one reason that immunotherapy has had so little success in the cure or chronic control of cancer in patients.

Tumor cells evolve that not only escape destruction by immune attack, but also that subvert normal immune cells to enhance tumor growth. Tumors recruit normal white blood cells to help in the process of tissue invasion.

Tumors also can release soluble factors that stimulate normal cells to produce enzymes that digest connective tissue and facilitate invasiveness. It's like renting bulldozers to clear space for new apartment houses.

The limitations of narrowly targeted therapy are also seen with cancer vaccines and immunotherapy. The earliest approaches at targeting tumor-specific molecules involved attempts to turn the immune system against proteins that are unique to cancer cells.

Certain types of lymphoma have a unique, patient-specific antibody on the surface of the lymphoma cells. The lymphoma cells make this antibody, which is absent from normal cells. Patients have been treated with antibodies targeted to the particular antibody on their lymphoma cells.

This antibody-against-an-antibody was prepared specially for each patient. In a study of 45 patients, eight responded. Only six patients had long-term control of their disease. The problem is that lymphoma cells can and do evolve without the surface antibody marker (Blood. 1998 Aug 15;92(4):1184-90).

Dr. Steven A. Rosenberg, Chief of Surgery at the National Cancer Institute (NCI) and a leading cancer immunologist, published a review of clinical trials on cancer vaccines. His analysis revealed that the overall response rate among 765 patients in a large number of different trials was only 3% (Nat Med. 2004 Sep;10(9):909-15).

Reference: "Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer" A. Glazier, et al. 2005

Immunological Research: A multi-faceted approach to curing disease

Gregory D. Pawelski

Last edited by gdpawel : 06-08-2013 at 12:21 PM. Reason: additional info
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