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Cancer immunotherapy, a collective term for several treatmentsThe treatment is not to be confused with the other treatments, and each of them has several different agents and regimens!

Cancer immunotherapy, as the name suggests, is a therapy that promotes the body's own immune system to better attack cancer cells.We should know that the immune system of the human body is very powerful, not only can kill bacteria, anti-virus, and exclude foreign organs, but also can inhibit and kill tumors, especially in the primary stage of tumorigenesis. However, these tenacious tumor cells do not die, they spend long years, gradually accumulate mutations, slowly break through the blockade of the immune system and other body regulatory systems, growing more and more and faster! This brings us to the middle to late stages of cancer, where the immune system is somewhat helpless. At this critical time, doctors who can give the immune system a hand by making it operate more aggressively and crazily (craziness comes at a price, often chewing up healthy tissue and producing toxic side effects) may be able to fight off the cancer's progression and even cure some patients. One of the limitations of this therapy is that it only targets tumors recognized by the immune system. So what kind of tumors are easily recognized? It's the old, porous tumors with lots of mutations that are so different from normal cells that are easy to recognize.

Cancer immunotherapy can be categorized into six main groups:

① Immunomodulatory drugs targeting T cells ② Other immunomodulatory drugs ③ Cancer vaccines ④ Cell therapy ⑤ Tumorolytic viruses

⑥ Bispecific antibodies targeting CD3

Here we focus on the two most commonCancer immunotherapy ① and ④:

One category is ④ "cellular immunotherapy".It is also called "biological immunotherapy" or "autologous blood activation therapy" or other names. In short, any cancer therapy with the word "biological" or "cellular" in it often refers to this type of cellular immunotherapy.

The most established and common cellular immunotherapy, theRelay T-cell therapyThe first step in the development of this therapy is the use of chimeric antigen receptor T-cell immunotherapy (CAR therapy, which is also called chimeric antigen receptor T-cell immunotherapy).CAR-T), after T-cells (a type of white blood cell) are drawn from the patient's body, these cells are genetically modified (also known as gene therapy, gene modification), forcing them to express the relevant receptors, so that they can specifically recognize tumor-associated antigens, thus completely activating their anticancer potential; they are then infused back into the patient's body.

On August 31, 2017The Food and Drug Administration (FDA) in the United States has approved the world's first over-the-counter T-cell therapy product.called Kymriah (tisagenlecleucel) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in children and young adult patients. It's a Novartis product, priced by the company at $475,000, with no additional billing for extracting the white blood cells.The FDA has also recommended a drug on the market, tocilizumab (Actemra, tocilizumab), for the treatment of the potentially drastic toxic side effects caused by Kymriah. (Additional billing is required.)

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FDA Official Web Page

October 2017FDA approves 2nd over-the-counter T-cell therapy product, named Yescarta (axicabtagene ciloleucel) for the treatment of non-Hodgkin's lymphoma, is made by Kite Pharmaceuticals and is priced by the company at $373,000, but extraction of white blood cells is billed separately.

In summary, this therapy has been listed in the United States for two kinds, which can be seen that its efficacy is still relatively good, but because this therapy only works in a small number of blood cancer patients, high cost, difficult to manage, high side effects, new therapies, it has not yet been listed in Europe and China for the time being. However, related efficacy studies and improvement studies are in full swing, and as of June 2016, there were 173 ongoing CAR-T clinical trials worldwide and 30 CAR-T clinical trials conducted in China. Experts predict that the Chinese market may not be available until after 2020. Of course, even if it goes on the market, the price is not affordable for ordinary people.

In addition to car-t, there are several therapies called TCR-T therapy, TAA/TSA (tumor-associated antigen/tumor-specific antigen)-targeted autologous circulating T-cell therapies, TIL therapies, T-cell therapies based on newer technologies (e.g., iPSCs, CRISPR, or gamma delta T-cells), NK/NKT cell therapies, and other types of cells such as macrophage or stem cell) therapies. These therapies are not described in detail here.

China Health Planning Commission statement: cellular immunotherapy still belongs to the clinical research stage; hospitals are prohibited from contracting departments in disguise; and medical advertisements are strictly scrutinized. Cellular immunotherapy shall cease to be applied to clinical treatment and be limited to clinical research. So if you want to try this therapy, patients can actively contact hospitals to participate in these clinical trials, without having to spend hundreds of thousands of dollars, or even basically free of charge, you can participate in clinical trials as a guinea pig (with the corresponding risks).

There is also a cancer immunotherapy calledImmune checkpoint therapy! That is, ① immunomodulatory drugs targeting T-cells

Instead of drawing blood, this treatment involves direct injection of monoclonal antibodies, which enter the blood and tissues and bind directly to the receptors on the surface of T cells. Some of the receptors on the surface of T-cells are called checkpoints, which are like the "tight bands" on the Monkey King's head. Once the monoclonal antibody binds to these receptors, it will loosen the tight bands and make the T-cells go crazy in the body, which is why it is called immune checkpoint therapy.。 This therapy is much more reliable, and there are several such drugs on the market in the US (but still in the approval stage in China!). .

For example, Keytruda (scientific name pembrolizumab), with 2016 sales of $1.4 billion, is FDA-approved for first-line treatment of certain lung cancers. A first-line drug is a drug of choice, which shows that its efficacy is very impressive.

Then there's Opdivo (scientific name nivolumab, $3.7 billion in sales in 2016)

The chart above is from a statistical report detailing the monoclonal antibody drugs in immune checkpoint therapies that bind the PD1 and PDl1 tightropes. There are a few other tightly bound drugs not listed here, such as ipilimumab, a monoclonal antibody drug that binds to the CTLA-4 receptor, which was approved by the FDA in 2011.

In a few years, these immune checkpoint antibody drugs will certainly enter the domestic market to benefit cancer patients. If you need them urgently now, there are also some special policies in the country, so you can learn about them from your doctor.

When treating cancer, doctors will inform in advance that radiotherapy and chemotherapy may not be able to get rid of the cancer cells completely, and the remaining cancer cells, if they break through the defense of the immune system, grow and multiply again on a large scale, which is often referred to as recurrence.Cellular immunotherapy, on the other hand, is a treatment that enhances the activity of the immune system, thereby reducing the risk of cancer recurrence and metastasis.

Below, "ask the doctor" will tell you more about it.

How does cellular immunotherapy work?

Immunotherapy is a new type of therapy used to treat cancer. Unlike traditional cancer treatments such as chemotherapy and radiotherapy, immunotherapy is a treatment that can stop the deterioration of cancer by stimulating the immune system to attack the cancer cells, and it cannot kill the cancer cells directly.

There are two main types of common immunotherapy:

(1) Checkpoint inhibitors

This method works by stopping the cancer cells from shutting down the immune system in order for the immune cells to continue attacking the cancer cells.

(2) Cell therapy

So-called cellular therapy involves removing some immune cells from the patient, genetically altering them so that they regain the ability to attack cancer cells, then replicating and multiplying them in a lab before delivering them back to the patient's body like a blood transfusion. This type of treatment needs to be made individually for each patient and is still experimental.

Cancer patients who want to improve their immunity can also start with these 4 aspects of life

(1) Active Exercise

According to their own health conditions, choose the appropriate exercise such as walking, jogging, swimming, boxing and dancing, etc., can improve their own immunity and increase the number of immune cells in the body. And regular exercise can also promote blood circulation, so that the immune cells work more efficiently.

(2) Healthy diet

The immune system, which is the guardian of health, also needs logistical supplies from the kitchen sink. A healthy immune system requires good nutrition. Studies have found that people living in poverty and suffering from malnutrition are more vulnerable to infectious diseases. There is some evidence that deficiencies in certain micronutrients affect the immune response process.

(3) Adequate sleep

Long-term sleep deprivation will significantly reduce the vitality of lymphocytes, and diseases will easily invade the body. If you want to be healthy, you must pay attention to sleep and try to ensure that you get 7-8 hours of sleep.

(4) Getting rid of negative emotions

It is estimated that many people have heard of this story: after a certain patient suffered from cancer, he positively looked away from everything, kept an optimistic mindset every day, and spent every day seriously. When he was rechecked, the cancer was miraculously shrunk. On the other hand, other patients in the same ward were in despair and grief every day, and the cancer, which was originally at an early stage, progressed rapidly and spread!

There is now a growing body of scientific research that has found that:Chronic stress stimulates the overproduction of inflammatory substances that can induce and aggravate cancer.

"Ask the Doctor" is a team of doctors from the ancient city of Xi'an.We share the most practical and scientific health knowledge for you, welcome to follow us!

Immunotherapy is the "fourth type of therapy" after the three traditional therapies of "surgery", "radiation therapy" and "drug therapy (anticancer agents, molecularly targeted drugs, etc.)". The "fourth type of therapy". Immunotherapy includes a variety of methods such as drugs that activate the function of immune cells, and treatment that involves the cultivation and proliferation of immune cells extracted from the patient's body in vitro and then injected back into the patient's body.

Lung cancer has always been a problem that bothers all of us, and the number of new cases of the disease is very large every year. In China, nearly 70% of lung cancer patients are already in advanced stages when they are diagnosed, and the most urgent need of this group of patients is to prolong their survival period.

Against this background, immunotherapy has become the hope that many lung cancer patients want to catch and has become a hot spot of attention. Immunotherapy is now very much in the limelight, not only in the academic world, but very many patients are also concerned about immunotherapy.

Immunotherapy has transformed the treatment of lung cancer. For advanced non-small cell lung cancer, immunotherapy has increased the 5-year survival rate of patients from about 5% to 16%. One of the biggest advantages of immunotherapy over traditional therapies is the durability of its efficacy and the fact that it has far fewer overall side effects than traditional radiotherapy.

That's not to say that PD-1 inhibitors are risk-free. About 5% of patients develop severe immune-related inflammatory reactions, including immune pneumonia, immune enteritis, immune hepatitis, and even immune myocarditis, in addition to pituitary gland inflammation and hypothyroidism in some patients. The above immune inflammation, if not detected in time and treated properly, is occasionally fatal. Therefore, when choosing PD-1 inhibitor therapy, it is also important to always keep the risks in mind and make sure it is done under the guidance and supervision of an experienced clinician.

Chemotherapy has a good side and of course a bad side compared to immunotherapy, for example, it has the potential to damage a person's immune function. So at present, it is more advocated to combine chemotherapy and immunotherapy, because immunotherapy such as PD-1 can enhance the positive effect of chemotherapy on the immune and reduce the side effect of chemotherapy on the immune.

Look at the survival curves of patients taking anticancer drugs compared to treatment with immunotherapy, data provided by theSendai Clinic, JapanProvided and not to be copied and reproduced.

People who are in need of Conradin NK cell immunotherapy

(1) Patients with tumors that require treatment to control or palliate their disease;

(2) Tumor patients who need to promote physical recovery, improve their physical condition, and need to be treated for their condition;

(3) To alleviate the pain of anticancer treatment, to treat residual cancer, and for patients who want to prevent cancer metastasis;

(4) Prevention of tumor recurrence and those who need combination therapy with immune cell therapy;

(5) The therapy helps to boost the body's immunity and is suitable for people with low immunity.

(6) In terms of cancer treatment, the average cost of cancer treatment at the Sendai Clinic in Japan is about250,000-300,000Between. That's why medical treatment abroad has been on the rise for many years, and the service population is still niche, at least for middle-class families and above, but it's not as "expensive" as rumors on the Internet make it out to be.

Sendai Clinic NK Cell Therapy, Japan

A treatment in which NK cells are taken from a patient's blood and proliferated to enhance attack, and then infused back into the body in the form of a drip.

Therapeutic Advantages:

①Combined with dendritic cell immunotherapy to further enhance cancer-fighting power.

② Low side effects, effectively preventing cancer cell recurrence and metastasis, and improving the quality of life of tumor patients.

Immunotherapy has entered a new era with the introduction of immune checkpoint inhibitors (IBIs), especially those that "unlock the immune brakes" by releasing the patient's autoimmune function.

Relationship between immune mechanisms and cancer

The immune system that protects our body will not only get rid of bacteria and viruses, but also cancer cells. However, cancer cells also evade the immune system's perception of them, or seek to survive and proliferate on their own by suppressing immune function.

White blood cells that assume immune function are multiply prepared to fight cancer cells

Immunity is a general term for the mechanism by which the body removes foreign substances from the body such as bacteria, viruses and cancer cells. Active in the immune system are white blood cells, which include neutrophils, macrophages, basophils, eosinophils, mast cells, dendritic cells, NK cells (Natural Killer Cells), T cells, B cells, etc., each of which has a different function.

Immunity is a God-given defense system, and there are two major categories: "natural immunity", which automatically eliminates foreign substances, and "acquired immunity", which obtains information from natural immunity, fights with a specific foreign substance, stores and remembers the information, and removes the foreign substance in response to its re-invasion (Figure 1), also known as "specific immunity". "also known as "specific immunity" (Figure 1). Another characteristic of immunity is that both natural and specific immunity can distinguish between "self" and "foreign body" under normal conditions, and the immune system only attacks the foreign body but not the self.

Initially, when a foreign body enters the body, the phagocytes (macrophages, neutrophils, etc.) that patrol the body begin to engulf the foreign body (called "antigens" in immunology) so that the foreign body does not cause more damage, which is also the process of natural immunity. When the macrophages and neutrophils are unable to handle it on their own, they pass the antigenic information to the dendritic cells.

In lung cancer treatment, the effective rate of PD-1 inhibitors alone is about 20%, and in order to further increase the effective rate, combination therapy is a big trend. At present, immunosuppressant combined with chemotherapy has been approved by FDA for first-line treatment, besides chemotherapy, other mainstream combination modalities are as follows:

1, Combining another immunotherapeutic agent: at present, PD-1 inhibitor combined with CTLA-4 antibody has been formally approved for malignant melanoma as well as renal cell carcinoma, for the study of PD-1 inhibitor combined with CTLA-4 antibody, at present, it also achieves better results in patients with advanced or recurrent non-small-cell lung cancer with TMB ≥10 mut/Mb. Regardless of the expression of PD-L1, the O drug + ibritumomab group to have more PFS benefit than patients in the chemotherapy group.

2、Combination radiotherapy: PD-1 inhibitors combined with radiotherapy is the combination of local and systemic treatment, which is also the future research direction. The clinical data of radiotherapy combined with immunotherapy is less, PACIFIC study applied immunotherapy to patients with stage III non-small cell lung cancer, and Durvalumab was given after synchronous radiotherapy to bring benefit to patients. However, the challenge is to avoid an increase in toxicity due to the combination of radiotherapy with immunization. The combination of radiotherapy and immunization requires balancing factors such as the dose of radiotherapy, duration, and sequence of treatment, and the answers to these questions are not yet clear. There are many trials underway and the results of the studies will have to wait.

3、Combination of targeted drugs: Current research data, whether primary or treated advanced non-small cell lung cancer ALK-positive patients, TKI inhibitors combined with immune checkpoint inhibitor therapy compared with single-agent TKI inhibitors efficacy results are not very satisfactory, so the follow-up also need more research to explore.

Although, advanced lung cancer is incurable, the current treatment has two objectives: one is to improve the quality of life of patients and the other is to prolong the survival time of patients. The treatment concept of advanced lung cancer should be the control of the disease rather than the elimination or cure of the disease. If the idea is to control the disease, the mindset will be much better.

immune systemThe human body is the "anti-virus software", not only can resist the invasion of viruses and bacteria, but also "repair system vulnerability", that is, to kill the human body's cancer cells and cells that may be cancerous. As the saying goes, "the road is high, the devil is high", the virus software will continue to change new tricks to prevent being recognized by the antivirus software, such as disguised as "good software". In the same way, the malignant cells in the human body will also "play this trick", disguised as a "good guy", so that the immune cells do not kill themselves. Immunotherapy is to increase the ability of immune cells to recognize and kill, and eliminate these "fake good guys".

Immunotherapy has existed for a long time, including interleukin-2 anti-cancer, DC-CIK therapy for the "Wei Zexi incident", and CAR-T therapy, all of which belong to the category of immunotherapy, however, when we say "immunotherapy", the first thing that comes to mind is definitely the most popular PD-1/PD-L1 and CLTA-4 immune target inhibitors. However, when we say the word "immunotherapy", the first thing that comes to mind is definitely the most popular PD-1/PD-L1 and CLTA-4 immune target inhibitors.

A knife can be used to kill an enemy, but it can also injure one's own people. So the body's immune cells are fitted with PD-1 and CLTA-4 proteins, like a headband on the Monkey King's head, to keep him from harming those who can recite the "spell".

Some cancer cells express PD-L1, just like the White Bone Monkey who learns the spell of "tightening the bands", and the PD-1/PD-L1 inhibitor destroys the White Bone Monkey's mouth or the Monkey King's ears, so that the golden bands clash loudly with the bones of the White Bone Monkey's skull!

CLTA-4The inhibitor was like removing the Monkey King's headband, so the golden rod and the skull of the White Bone Demon once again made a loud crash!

Let me be serious one last time, although the story ends with a loud clash between the golden rod and the skull of the white bone spirit! However, the mechanisms of PD-1/PD-L1 and CLTA-4 inhibitors are slightly different, with the former increasing the "recognition" ability of immune cells and the latter enhancing the "killing" ability.

One aspect of treatment for cancer is removal. The other aspect is killing the cancer cells with chemotherapy. As for immunotherapy using immune modulation, he believes that the immune cells will gobble up the cancer cells. This kind of thinking is cruel to the patient. Enduring a double torture. The final solution is all about death.

In recent years, with the development of medical science and technology, the means of treating cancer and drugs are also iterative, and the current more popular ways of treating cancer include interventional therapy, immunotherapy and so on. It has brought more gospel as well as hope to patients. Immunotherapy is mainly to attack tumors through one's own immune system.

Scientists have found that although most tumors can trigger a response from the immune system, some tumors are still able to evade detection by the immune system and spread in patients with normal immune function. Mainstream immunotherapy is a therapy that activates the body's own immune system to resist and destroy cancer cells, allowing the body's own immune cells to kill the cancer cells.

Learn more about interventional therapy by following [He Xiaofeng, Ozone Interventionist】

The immune system of the human body is mainly composed of bone marrow, lymph nodes and tonsils, which are immune organs and tissues, and the cells with immune function are lymphocytes, platelets and mononuclear phagocytes. The immune system is equivalent to a barrier of the human body, able to resist the attack of foreign viruses, bacteria and cancer cells, and maintain the stability of the body. Cancer immunotherapy mainly refers to a variety of immune methods to help the body's immune system recognize cancer cells and molecules, and strengthen the immune response to destroy cancer. There are usually two types of cancer immunotherapy: 1. Stimulate or strengthen the efficacy of one's own immune system to fight against cancer: Biological immunotherapy can be used, which is to extract normal cells from our body, activate and multiply them, and finally implant them into the body to the extent of matching with the body's immune system, so as to destroy the purpose of spreading cancer cells. It can treat advanced cancer, but it is better to cooperate with some other treatments so as to have better therapeutic effect. 2. Adding new components to the immune system, such as proteins for the artificial immune system, such as using antibodies and vaccines. For example, monoclonal antibodies are injected that can specifically attack a certain part of the cancer cells, and the treatment needs to be given through an intravenous injection. However, it is important to note that antibodies themselves are proteins, and these types of antibodies can sometimes cause allergic reactions, which are especially common when given for the first time. Possible side effects include fever, chills, weakness, headache, nausea and vomiting, diarrhea, low blood pressure, and rash. There is also the use of cytokines such as interleukin 2 or interferon, which are fed into the body to boost the immune response and kill cancer cells.

Cancer immunotherapy must consider 60 million negative oxygen ions, rapid inhibition of the spread of cancer cells, repair dna damage, so that nerve conduction to return to the transmission function, improve immunity, repair cell damage, the body needs cell regeneration is normal, so that the blood and body fluids to restore the weak alkaline. Simply put, it is a comprehensive stimulation of the body's self-healing system. Maintain an optimistic state of mind, increase the ionic dish anti-cancer factor nutrient absorption can be. In two years there will be harvest surprise effect, after all, cancer is many years of accumulation of chronic disease, not a day and a half months to the acute disease.

Negative oxygen ions are essential for cancer recovery. Just be aware of it.

It is to stimulate your body's immunity to remove cancer cells in some way. The most primitive method comes from a folk doctor in the United States, using E. coli bacteria to stimulate the body's high fever, so as to achieve the purpose of removing cancer cells, of course, this kind of success rate is not high, because most of the patients died before the fever, this situation is very easy to explain with the theory of traditional Chinese medicine.