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Immunotherapy is one of the most exciting areas of new discoveries and treatments for many different kinds of various diseases such as cancer. Understanding how the immune system works is opening the doors to developing new treatments that are changing the way we think about and treat some diseases.

Immunotherapy is the prevention or treatment of a disease with substances that stimulate the immune response. It is also called biological therapy and now mostly used in cancer treatment by harnessing the ability of the body’s immune system to combat infection or disease. It is designed to boost the body's natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function.

Our immune system is a network of cells, tissues and organs that works together to recognize and destroy foreign invaders such as bacteria and viruses or abnormal or unhealthy cells in our bodies. The most important function of the immune system is to know the difference between self and non-self. Self means our own body tissues. Non-self means any abnormal cell or foreign invader, such as bacteria, viruses, parasites and fungus. Normally, our immune system will not attack anything that it identifies as a healthy part of self. The problem with cancer cells is that they arise from our cells, but there are differences. As they grow and spread, cancer cells undergo a series of changes, or mutations, becoming increasingly less like normal cells. Sometimes our immune system can detect these differences and respond. Other times, the cancer cells slip through the defenses or are actually able to inhibit the immune system. Researchers have known for many years that our immune systems do recognize and attack cancer cells. But, the progress being made in recent times in immunotherapy is the result of new understanding about the complex interaction between the immune system and cancer. The goal of the field of immuno-oncology, also known as tumor immunology, is to understand exactly how the immune system interacts with the cancer, and then use that information to develop new immunotherapy treatments.

Immunotherapy often uses substances referred to as biological response modifiers (BRMs). The body usually only produces small amounts of these BRMS in response to infection or disease, but in the laboratory, large amounts of these BRMs can be generated in order to provide a therapy for cancer, rheumatoid arthritis and other illnesses.

Examples of immunotherapies include monoclonal antibodies, interferon, interleukin-2 (IL-2), and colony-stimulating factors CSF, GM-CSF and G-CSF. Interferon is currently being used to treat hepatitis C and is also being tested, along with IL-2 as a treatment for advanced malignant melanoma. Immunotherapy is being investigated as a means of blocking the inflammation seen in conditions such as Chron’s disease and rheumatoid arthritis.

Immunotherapy may work by stopping or slowing the growth of cancer cells or stopping cancer from spreading to other parts of the body or helping the immune system work better at destroying cancer cells.

There are several types of immunotherapy which include

(1) Monoclonal antibodies:

When the body’s immune system detects something harmful, it produces antibodies. Antibodies are proteins that fight infection.

Monoclonal antibodies are a specific type of therapy made in a laboratory. They are designed to attach to specific proteins in a cancer cell. These therapies are highly specific, so they do not affect cells that do not have that protein.

Monoclonal antibodies are used as cancer treatments in various ways:

To allow the immune system itself to destroy the cancer cell. The immune system doesn't always recognize cancer cells as being harmful. This is one of the ways that cancer can grow and spread. Researchers have identified the PD-1 pathway as being critical to the immune system’s ability to control cancer growth. Blocking this pathway with PD-1 and PD-L1 antibodies can stop or slow cancer growth. These immunotherapy drugs may be referred to as checkpoint inhibitors because they interrupt an important part of the immune system process. Examples of checkpoint inhibitors include ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda). Additional drugs are being studied.
To deliver radiation directly to cancer cells. This treatment, called radioimmunotherapy, uses monoclonal antibodies to deliver radiation directly to cancer cells. By attaching radioactive molecules to monoclonal antibodies in a laboratory, they can deliver low doses of radiation specifically to the tumor while leaving healthy cells alone. Examples of these radioactive molecules include ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar).

Diagnose cancer. Monoclonal antibodies carrying radioactive particles may also help diagnose certain cancers, such as colorectal, ovarian, and prostate cancers. Special cameras identify the cancer by showing where the radioactive particles build up in the body. In addition, a pathologist may use monoclonal antibodies to determine the type of cancer a person may have by analyzing the sample of tissue removed during a biopsy. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease.
Carry drugs directly to cancer cells. Some monoclonal antibodies carry other cancer drugs directly to cancer cells. Once the monoclonal antibody attaches to the cancer cell, the treatment it is carrying enters the cell. This causes the cancer cell to die without damaging other healthy cells. One example is Brentuximab vedotin (Adcetris), a treatment for certain types of Hodgkin and non-Hodgkin lymphoma. Another example is trastuzumab emtansine or TDM-1 (Kadcyla), which is a treatment for HER2-positive breast cancer.

(2) Non-specific immunotherapies:

Like monoclonal antibodies, non-specific immunotherapies also help the immune system destroy cancer cells. Most non-specific immunotherapies are given after or at the same time as another cancer treatment, such as chemotherapy or radiation therapy. However, some non-specific immunotherapies are given as the main cancer treatment.

Two common non-specific immunotherapies are:

Interferons. Interferons help the immune system fight cancer and may slow the growth of cancer cells. An interferon made in a laboratory, called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]), is the most common type of interferon used in cancer treatment. Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair.
Interleukins. Interleukins help the immune system produce cells that destroy cancer. An interleukin made in a laboratory, called interleukin-2, IL-2, or aldesleukin (Proleukin), is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, which can be treated with other medications. Some people may also experience flu-like symptoms.

(3) Cancer vaccines:

Using vaccine is another method used to help the body fight disease. A vaccine exposes the immune system to an antigen. This triggers the immune system to recognize and destroy that protein or related materials. There are two types of cancer vaccines: prevention vaccines and treatment vaccines.

Prevention vaccine. A prevention vaccine is given to a person with no symptoms of cancer. It is used to keep a person from developing a specific type of cancer or another cancer-related disease. For example, Gardasil and Cervarix are vaccines that prevent a person from being infected with the human papillomavirus (HPV). HPV is a virus known to cause cervical cancer and some other types of cancer. Some doctors advice that all children should receive a vaccine that prevents infection with the hepatitis B virus. A hepatitis B infection may cause liver cancer.
Treatment vaccine. A treatment vaccine helps the body's immune system fight cancer by training it to recognize and destroy cancer cells. It may prevent cancer from coming back, eliminate any remaining cancer cells after other types of treatment, or stop cancer cell growth. A treatment vaccine is designed to be specific, which means it should target the cancerous cells without affecting healthy cells. At this time, sipuleucel-T (Provenge) is the only treatment vaccine approved. It is designed for treating metastatic prostate cancer. Additional cancer treatment vaccines are still in development and only available through clinical trials.

(4) Oncolytic virus therapy:

Oncolytic virus therapy is a new type of immunotherapy that uses genetically modified viruses to kill cancer cells. First, the doctor injects a virus into the tumor. The virus enters the cancer cells and makes copies of itself. As a result, the cells burst and die. As the cells die, they release cancer antigens. This triggers the patient’s immune system to launch an attack on all cancers cells in the body that have those same antigens. The virus does not enter healthy cells.

The doctor can inject genetically modified virus directly into melanoma lesions that a surgeon cannot remove. Patients receive a series of injections until there are no lesions left. Side effects can include fatigue, fever, chills, nausea, flu-like symptoms and pain at the injection site.

These side effects are generally short-term, but patients may need to stay in hospital if they develop severe problems.

Other areas where immunotherapy is being used...

Allergen immunotherapy

Also known as allergy shots, is a form of long-term treatment that decreases symptoms for many people with allergic rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy.

Chron’s disease

There is currently no treatment that can cure Chron’s disease, but advances in mucosal immunology have led to the discovery of a wide range of new targets for resolving the inflammation seen in this condition. Research suggests that the intestinal inflammation starts because of an aberrant response by the innate immune system that is eventually driven by T cells. Current therapies are focused on inhibiting, altering or suppressing T-cell differentiation and in some parts of the world, the medications azathioprine or mercaptopurine are the most frequently used.

In cases of severe Chron’s disease that is not helped by these drugs, two biological therapies are available that may be used to treat the condition. These powerful immunosuppressants are called infliximab and adalimumab and both work by targeting a protein called tumor-necrosis factor-alpha (TNF-α). TNF- α is a cell signalling protein (cytokine) secreted by T-helper-1 cells that has been shown to play a critical role in the inflammation process seen in Chron’s disease.

Infliximab is administered via intravenous infusion in hospital and adalimumab can be administered via an injection, which the patient or a family member may be able to learn to do themselves.

Rheumatoid arthritis

Rheumatoid arthritis can be treated with disease-modifying antirheumatic drugs (DMARDS) to slow progression of the disease and prevent permanent damage in the joints and other tissues. Examples of these DMARDs include methotrexate, hydroxychloroquine and sulfasalazine. However, in cases where methotrexate or other DMARDs fail to ease symptoms and inflammation, a biological therapy may be recommended to block certain parts of the immune system that contribute to inflammation in this condition. Biological treatments such as etanercept, infliximab or certolizumab are usually taken in combination with a DMARD. They are administered via injection and stop chemicals in the blood from activating an immune response that attacks the joints.

Type I Diabetes

There are two main types of diabetes -
Type 1 - where the pancreas does not produce any insulin
Type 2 - where the pancreas does not produce enough insulin - or the body's cells do not react to insulin

In type 1 diabetes the immune system destroys the cells that make insulin, the hormone needed to control blood sugar levels. The hope is the immunotherapy treatment will re-train or reset the immune system. Volunteer patients that have agreed to take part in the trials that are being conducted now are being given injections that contain peptides - small fragments of protein molecules found in the insulin-producing beta cells of the pancreas. Volunteers will receive six injections, four weeks apart.
It is hoped these will prompt T regulatory cells in the immune system to mount a protective response to the beta cells, so re-training the immune system is the main aim here. If the scientists can teach the immune system to stop attacking the insulin-producing beta cells in the pancreas we can potentially prevent type 1 diabetes from developing.

Although most of these therapies are in experimental stages, they are proved to be highly promising till now and when scientists working in the area iron out the problems like side effects and limitations of the use of this technology that are still bothering them, this area is one of the most interesting and exciting in therapy research and can take us to new  horizons in dreadful disease cure, control and prevention.

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Replies to This Discussion


How Universal cancer vaccine is 'found'...

Recently Scientists have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumours as if they were a virus.

Writing in Nature, an international team of researchers described how they had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease.

The patients' immune systems responded by producing "killer" T-cells designed to attack cancer.

The vaccine was also found to be effective in fighting “aggressively growing” tumours in mice.

Such vaccines are fast and inexpensive to produce, and virtually any tumour antigen [a protein attacked by the immune system] can be encoded by RNA.

The nanoparticulate RNA immunotherapy approach introduced here may be regarded as a universally applicable novel vaccine class for cancer immunotherapy.

Three patients were given low doses of the vaccine and the aim of the trial was not to test how well the vaccine worked. While the patients' immune systems seemed to react, there was no evidence that their cancers went away as a result.

In one patient, a suspected tumour on a lymph node got smaller after they were given the vaccine. Another patient, whose tumours had been surgically removed, was cancer-free seven months after vaccination.

The third patient had eight tumours that had spread from the initial skin cancer into their lungs. These tumours remained “clinically stable” after they were given the vaccine.

The vaccine, which used a number of different pieces of RNA, activated dendritic cells that select targets for the body's immune system to attack. This was followed by a strong response from the "killer" T-cells that normally deal with infections.

Cancer immunotherapy is currently causing significant excitement in the medical community.

It is already being used to treat some cancers with a number of patients still in remission more than 10 years after treatment.

While traditional cancer treatment for testicular and other forms of the disease can lead to a complete cure, lung cancer, melanoma, and some brain and neck cancers have proved difficult to treat.

Being able to inject an effective treatment into a patient’s bloodstream would be a significant step forward. The vaccine also produced limited flu-like side-effects in contrast to the extreme sickness caused by chemotherapy.

This new study, in mice and a small number of patients, shows that an immune response against the antigens within a cancer can be triggered by a new type of cancer vaccine.

Although the research is very interesting, it is still some way away from being of proven benefit to patients.

In particular, there is uncertainty around whether the therapeutic benefit seen in the mice by targeting a small number of antigens will also apply to humans, and the practical challenge of manufacturing nanoparticles for widespread clinical application.

However, more research is needed in a larger number of people with different cancer types and over longer periods of time before we could say we have discovered a ‘universal cancer vaccine’. But this research is a very positive step forwards towards this global goal.




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