Cancer immunotherapy

 Cancer immunotherapy
From Wikipedia, the free encyclopedia



Cancer immunotherapy is the use of the immune system to treat cancer. There are three main groups of immunotherapy used to treat cancer: cell-based therapies, antibody therapies and cytokine therapies. They all exploit the fact that cancer cells often have subtly different molecules on their surface that can be detected by the immune system. These molecules, known as cancer antigens, are most commonly proteins but also include other molecules such as carbohydrates. Immunotherapy is used to provoke the immune system into attacking the tumor cells by using these cancer antigens as targets.

Cell-based therapies, also known as cancer vaccines, usually involve the removal of immune cells from someone with cancer, either from the blood or from a tumor. Immune cells specific for the tumor will be activated, grown and returned to the person with cancer where the immune cells provoke an immune response against the cancer. Cell types that can be used in this way are natural killer cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells. The only cell-based therapy currently approved for use is Dendreon's Provenge, which is used for the treatment of prostate cancer.

However, Antibody therapies are currently the most successful form of immunotherapy, with many approved treatments for a wide range of cancers. Antibodies are proteins produced by the immune system that bind to a target antigen on the surface of a cell. In normal physiology they are used by the immune system to fight pathogens. Each antibody is specific to one or a few proteins and those that bind to cancer antigens are used in the treatment of cancer. Cell surface receptors are common targets for antibody therapies and include the epidermal growth factor receptor and HER2. Once bound to a cancer antigen, antibodies can induce antibody-dependent cell-mediated cytotoxicity, activate the complement system, prevent a receptor interacting with its ligand or deliver a payload of chemotherapy or radiation; all of which can lead to cell death. There are twelve antibodies currently approved for the treatment of cancer: Alemtuzumab, Bevacizumab, Brentuximab vedotin, Cetuximab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Ipilimumab, Ofatumumab, Panitumumab, Rituximab, Tositumomab and Trastuzumab.

Interleukin-2 and interferon-α are examples of cytokines; proteins that regulate and coordinate the behaviour of the immune system. They have the ability to enhance the anti-tumor activity of the immune system and thus can be used as treatments in cancer. Interferon-α is used in the treatment of hairy-cell leukaemia, AIDS-related Kaposi's sarcoma, follicular lymphoma, chronic myeloid leukaemia and malignant melanoma. Interleukin-2 is used in the treatment of malignant melanoma and renal cell carcinoma.




Cytokine therapy
Cytokines are a broad group of proteins produced by many types of cells present within a tumor. They have the ability to modulate immune responses and are often utilised by the tumor to allow it to grow and manipulate the immune response. These immune-modulating effects allow them to be used as drugs to provoke an immune response against the tumor. Two commonly used groups of cytokines are the interferons and interleukins.[70]
Interferon[edit]

Interferons are cytokines produced by the immune system usually involved in anti-viral response, but also have use in the treatment of cancer. There are three groups of interferons (IFNs): type I (IFNα and IFNβ), type 2 (IFNγ) and the relatively newly discovered type III (IFNλ). IFNα has been approved for use in hairy-cell leukaemia, AIDS-related Kaposi's sarcoma, follicular lymphoma, chronic myeloid leukaemia and melanoma. Type I and II IFNs have been researched extensively and although both types promote the anti-tumor effects of the immune system, only type I IFNs have been shown to be clinically effective in cancer treatment. IFNλ has been tested for its anti-tumor effects in animal models, and shows promise.[71][72]
Interleukins[edit]

Interleukins are a group of cytokines with a wide array of effects on the immune system. Interleukin-2 is used in the treatment of malignant melanoma and renal cell carcinoma. In normal physiology it promotes both effector T cells (cells that produce the immune response) and T-regulatory cells (cells that repress the immune response), but its exact mechanism in the treatment of cancer is unknown.[70][73]

NOW THE NATURAL ROUTE....

 Plants, fungi, bacteria and marine organisms are potential sources of anti-cancer drugs. Plants and bacteria have been the most successful sources of drugs, which include anthracycline, the taxanes and vinca alkaloids. These drugs intercalate DNA and are known as cytotoxic drugs. In addition to these kinds of drugs, natural products are also known to stimulate the immune system, which can be utilized in the treatment of cancer.[79]

Certain compounds in medicinal mushrooms, primarily polysaccharide compounds, can up-regulate the immune system and have anti-cancer properties. Beta-glucans, such aslentinan, are known as "biological response modifiers", and their ability to activate the immune system is well documented. Specifically, beta-glucans stimulate the innate branch of the immune system. Research has shown beta-glucans have the ability to stimulate macrophage, NK cells, T cells, and immune system cytokines. The mechanisms in which beta-glucans stimulate the immune system is only partially understood. One mechanism in which beta-glucans are able to activate the immune system, is by interacting with theMacrophage-1 antigen (CD18) receptor on immune cells.[80] Agaricus subrufescens, (often mistakenly called Agaricus blazei), Lentinula edodes (Shiitake mushrooom), Grifola frondosa and Hericium erinaceus are fungi known to produce beta-glucans and have been tested for their anti-cancer potential.[79] Polysaccharide-K, isolated from Trametes versicolor, is another polysaccharide that has anti-cancer properties.[81][82]

Japan's Ministry of Health, Labour and Welfare approved the use of Polysaccharide-K (produced by Coriolus versicolor) in the 1980s, to stimulate the immune systems of patients undergoing chemotherapy.[82] In Australia, a pharmaceutical based on a mixture of several mycological extracts including lentinan and Polysaccharide-K is sold commercially as MC-S.


Summary:
I use the above and below ideas (like immune system modulation) and find all readily available products that are not expensive on Lucy's Tippner Cancer Protocol that are found to have those properties.






 New and future immunotherapies
Anti-CD47 antibodies[edit]
Anti-CD47 antibodies, which block the protein CD47 from telling the cancer's host human immune system not to attack it, have been shown to eliminate or inhibit the growth of a wide range of cancers and tumors because CD47 is present on all known cancer cells (it is also present on many healthy cells of the body). After the cancer cells have been engulfed by macrophages, the host immune system's CD8+ T Cells become mobilized against the cancer and attack it on their own in addition to the macrophages, producing a personalized attack on virtually any form of cancer. When the immunotherapy technique was tested on human tumors transplanted in to mice, it stopped the spread of cancer 90 percent of the time and often eliminated all signs of the cancer. Phase 1 human trials are set to begin in 2014.[74][75][76]

Anti-GD2 antibodies


The GD2 ganglioside
Carbohydrate antigens on the surface of cells can be used as targets for immunotherapy. GD2 is a ganglioside found on the surface of many types of cancer cell including neuroblastoma, retinoblastoma, melanoma, small cell lung cancer, brain tumors, osteosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, liposarcoma, fibrosarcoma, leiomyosarcoma and other soft tissue sarcomas. It is not usually expressed on the surface of normal tissues, making it a good target for immunotherapy to allow for specific action against the tumor and reduced toxicity. Phase I, II, and III trials are underway for antibody treatments that bind to this antigen.[77]

Immune checkpoint blockade
A ligand-receptor interaction that is currently being investigated as a target for cancer treatment is the programmed cell death 1 (PD-1; also known as CD279) and PD-1 ligand 1 (PD-L1). In normal physiology PD-L1 on the surface of a cell binds to PD1 on the surface of an immune cell, which inhibits the activity of the immune cell. It appears that upregulation of PD-L1 on the cancer cell surface may allow them to evade the host immune system by inhibiting T cells that might otherwise attack the tumor cell. Antibodies that bind to either PD-1 or PD-L1 and therefore block the interaction may allow the T-cells to attack the tumor.

EGF receptor antibodies
Other anti-EGFR monoclonal antibodies in development include: ABX-EGF, hR3, and EMD 72000. Although they hold significant promise for the future, none of the agents are currently beyond phase I clinical trials.



Lucy never did radiation or chemo, she only did the Tippner Protocol. The Tippner Cancer Protocol combines immunotherapy and molecular cancer therapy using off the shelf readily available inexpensive natural substances. She is past 3 years after diagnosis by biopsy

I buy most of the stuff from Swanson Vitamins. They are cheaper, in capsules for dosage changes, and carry almost everything I give to Lucy except for the Chinese Herbs Stasis Breaker prescription, and the Low Dose Naltrexone prescription. Here is a $5 off coupon link I found

Cancer of the Nasal and Paranasal Sinuses in Dogs

 Nasosinal Tumors

Description – Tumors of the nasal cavity and paranasal sinuses consist of 1% of all canine neoplasms. The intranasal lesions mostly manifest themselves as adenocarcinoma, squamous cell carcinoma and undifferentiated carcinoma. The remaining, however, comprise fibrosarcoma, chondrosarcoma, osteosarcoma and undifferentiated sarcoma. Among them carcinomas and sarcomas are the most aggressive. At the time of diagnosis the rate of metastasis is usually low but at the time of death it is around 40% to 50%. The common metastatic sites are the regional lymph nodes and the lungs whereas the less common sites include the bones, kidneys, liver, skin and brain.

 Benign tumors like polyps and fibromas too have been found.

The average age of dogs with nasosinal tumors is 10 years. A predilection has been reported among medium and large breeds. 


Nasal Adenocarcinoma in Dogs

Nose cancer (or nasal adenocarcinoma) occurs when too many cells in the animal's nasal and sinus passages come together. The disease progresses slowly and occurs both in dogs and cats. Studies have shown nose cancer is more common in larger animal breeds than in smaller ones, and it may be more common in males than females. Options exist when the disease is caught early and aggressively treated.


Chondrosarcoma of the Nasal and Paranasal Sinuses in Dogs

A chondrosarcoma (CSA) is the second most common primary tumor in dogs, accounting for ten percent of all primary bone tumors. This is a malignant, invasive and fast spreading tumor in dogs. A CSA of the nasal and paranasal sinuses arises from the mesenchymal tissue, a connective collagenous tissue that is found throughout the body, and metastasizes to other parts of the body, including the nasal bones. It usually occurs on one side of the nasal cavity and extends to the other side over time.


Nasal Squamous Cell Carcinoma in Dogs

Both the inside of the nose and the paranasal sinuses are covered in the same type of tissue, called the epithelium. The outer layer of this tissue is scale like, and is called the squamous epithelium. Tumors that grow from this squamous epithelium are called squamous cell carcinomas.

Squamous cell carcinomas are the second most common type of nasal tumor that dogs get. They usually grow slowly over several months. Most commonly, they occur on both sides of the nose, and it is common for this kind of cancer to spread to the bone and tissue near it. In some cases, this type of nasal tumor will spread to the brain, causing seizures. Squamous cell carcinomas in the nose and sinuses are usually seen in dogs over nine years old, but they have been seen in dogs as young as three years old.

Diagnosis

Your veterinarian will need a complete background medical history leading up to your dog's disease symptoms. Routine blood tests include a complete blood count, biochemistry profile, urinalysis and platelet count. The results may show normal levels. Your veterinarian will also examine the blood samples for evidence of fungal or bacterial infections. Aspergillus is sometimes found in dogs with nasal tumors.

Radiographic studies can be helpful in confirming the diagnosis, but even this type of diagnostic method is challenging. Computed tomography (CT) scans and magnetic resonance imaging (MRI) will often produce a more substantial image of the extent of invasion. An endoscope -- a tubular device with an attached camera that allows for a closer look at the diseased area -- can also be used examine the internal structure of the nasal canal, and may also be used to collect tissue specimens for biopsy, but because of the small space, this can be difficult. Other methods for collecting tissue and fluid samples may be employed, including fine needle aspiration, and suction. Biopsy is the only way to conclusively diagnose nasal cancer.

Your veterinarian may also take radiographs of other areas of the body to evaluate if metastasis is taking place.



Causes – The etiology of nasosinal tumors is largely unknown but some reports suggest that animals living in urban areas are at an increased risk. This is primarily due to the nasal filtering of pollutants. Exposure to passive smoking and fossil fuel combustion products like those produced by coal or kerosene heaters may accentuate the risk of this type of cancer.

Symptoms – Some of the most common clinical signs may include epistaxis (bloody nasal discharge), mucopurulent discharge (nasal discharge containing mucous and pus), facial deformity from bone erosion and subcutaneous extension of the tumor, sneezing, dyspnea (shortness of breath) or stertorous breathing (harsh noisy breathing), exophthalmus (abnormal protrusion of the eye) and ocular discharge due to obstruction of the nasolacrimal duct (carries tears from the lacrimal sac into the nasal cavity).

On rare occasions animals with large tumors involving the caudal region of the nasal cavity may have neurological signs including seizures, behavioral changes, paresis (partial loss of movement), circling and obtundation (dog that does not have full mental capacity).



Treatment – By the time nasal carcinoma is detected, the disease has already become highly infiltrative. The degenerative nature of the disease and its critical location of the tumor near the brain and eyes renders it non-amenable to treatment and makes surgery impossible.  So, radiation therapy using high-energy mega voltage equipment is the only conventional treatment of choice for nasosinal tumors. It covers the entire nasal cavity, including, bone.

However, radiation has many disadvantages. The side effects of irradiation vary with protocols. Acute toxicities that result from irradiation include oral mucositis (inflammation and ulceration of the mouth), rhinitis (running nose), desquamation (shedding of the outer layers of the skin) and keratoconjunctivitis (inflammation of the cornea and conjunctiva) and blepharitis (ocular disease characterized by inflammation of the eyelid margins).

This state of affairs continue for 2-8 weeks after therapy for which oral antibiotics and pain medications are prescribed. However, if oral mucositis, attains severe proportions, esophagostomy (surgical opening into the esophagus) and gastrostomy (surgical opening into the stomach) tube feedings may be needed in the short term.

Sometimes the side effects of radiation may set in late. But they can be even more dangerous than the acute ones. These may include cataracts (cloud that develops in the crystalline lens of the eye), keratitis (condition in which the cornea of the eye becomes inflamed), atrophy (wasting away of the part of the body), keratoconjunctivitis, anterior uvea, hemorrhage, degeneration, brain necrosis (brain death), seizures, optic nerve degeneration, osteonecrosis (bone collapse) and fibrosis (development of excess fibrous connective tissue in an organ). Some complications develop late after therapy and are generally non-treatable.

Prognosis – Without treatment the prognosis for nasal carcinoma is approximately 3 months. The median survival time of dogs with epistaxis is 88 days whereas those without epistaxis is 224 days. The median survival time after surgery is 3-6 months. The median survival time with high voltage irradiation is 8-19.7 months.


Lucy received no radiation nor chemotherapy. She only received the Tippner Cancer Protocol. She is now past 3 years since diagnosis by biopsy of nasal adenocarcinoma and has virtually no symptoms.







Lucy never did radiation or chemo, she only did the Tippner Protocol. The Tippner Cancer Protocol combines immunotherapy and molecular cancer therapy using off the shelf readily available inexpensive natural substances. She is past 3 years after diagnosis by biopsy

I buy most of the stuff from Swanson Vitamins. They are cheaper, in capsules for dosage changes, and carry almost everything I give to Lucy except for the Chinese Herbs Stasis Breaker prescription, and the Low Dose Naltrexone prescription. Here is a $5 off coupon link I found