For clinical treatments of general diseases, safety is considered first, followed by efficacy, cost, and so on. In cancer treatment, the order of choices may be different because the patient's goal of survival is more explicit. The treatment of cancer is more based on the principle of maximizing the survival period and quality of life of patients. Surgery, chemotherapy, and radiation therapy are the three well-known standard treatments for cancer, and immunotherapy has been called the "fourth treatment" for cancer.

Compared with the traditional standard therapies, immunotherapy has not been used for a long time, but it has started from the "fundamental mechanism of cancer occurrence", created a new direction of treatment, and achieved many remarkable results, and is now getting more and more attention from patients and the medical profession, especially the introduction of PD1, which has brought new hope to some cancer patients. In particular, the introduction of PD1 has brought new hope to some cancer patients and changed the thinking of traditional treatment.

Part 1: Why do people get cancer?

Beginning with the origin of cancer, there are about 40 to 60 trillion cells in the human body, with about 100 million new and old cells alternating every minute. When the human body replicates new cells, some of the replication will be biased, and the cells that fail to replicate are considered "cancer cells" (some cells are infected by viruses). Each adult produces about 3,000-5,000 new "cancer cells" per day, and at the same time, the body's immune system eliminates them, thus achieving a balance and maintaining the normal state of the body. It is only when the power of the cancer cells exceeds the power of the immune cells that the body loses its balance and develops cancer. The battle between cancer cells and the immune system is scientifically known as "Immuno-editing". The entire process usually spans a decade, if not decades.

First step: immune clearance

The immune system is so strong that if one cancer cell comes out, it kills it.

Step 2: Immune balance

"Social unrest", cancer cells keep popping up, the immune system is busy, keeps killing, but can't get rid of the roots.

Step 3: Immune Escape

The immune system fails, and the cancer cells escape regulation and even turn on the immune system, aiding and abetting the cancer. This is when we see cancer.

The second of these steps takes the longest. Studies have found that cancer cells can develop an "immune balance" with the immune system that lasts for decades. Although this was previously only a hypothesis, with advances in medical technology there is now more and more evidence that it exists.

Part.2 What is immunotherapy?

Immunotherapy is a method of treating cancer by utilizing the innate immune function of human beings. The patient's own immune cells are extracted, cultured in vitro to make the cells more vigorous and multiply, and then injected back into the patient's body so that the powerful immune cells can fight against the cancer cells.

Part.3 Indications for immunotherapy

Except for some leukemias and some malignant lymphomas, immunotherapy is basically applicable to all cancers, including advanced cancers and other hard-to-treat cancers. Even for metastatic recurrent cancers that are difficult to be treated by surgery, chemotherapy and radiotherapy, it is possible to achieve the effect of shrinking cancer lesions, inhibiting the development of cancer, or even making cancer cells disappear completely through immunotherapy. In addition, immunotherapy can also be used for the prevention of postoperative recurrence and metastasis.

Immunocell therapy can be used in combination with surgery, chemotherapy, and radiotherapy. Because it uses autologous immune cells, it has fewer side effects and better therapeutic effects to look forward to, as well as relieving the side effects of chemotherapy, thus maximizing the quality of survival of cancer patients.

Part.4 The current situation of immunotherapy in China

Immunotherapy in China started late and is still in the clinical research stage, and immunotherapy was once pushed into the limelight in 2016, and many patients and their families are skeptical and wait-and-see attitude towards immunotherapy.

The National Health Planning Commission recently said in an interview with the media: the domestic immunotherapy is still immature, although it can make the overall survival of patients significantly longer, quality of life significantly improved, but because there are still problems such as uneven quality of cell preparation, specificity is not strong, individual efficacy varies greatly, and does not yet have the conditions for further widespread clinical application, but at the same time, the Commission also emphasized that the therapeutic prospect of immune cells The company has also emphasized that the prospect of immune cell therapy is broad.

Part.5 ? About dendritic cells

Winner of the 2011 Nobel Prize in Physiology and Medicine

Discoverer of dendritic cells

-Dr. Ralph Steinman, the founder of the dendritic cells, has been working on the development of dendritic cells for many years. Dr. Ralph Marvin Steinman

Dr. Ralph Marvin Steinman is an internationally renowned immunologist and cell biologist, who discovered the "dendritic cell" and its basic mechanism in 1973 together with Dr. Zanvil. He was awarded the Nobel Prize in Physiology and Medicine on October 3, 2011.

Note: Dendritic cells used in immunotherapy are derived from monocytes in the body's own blood, and are responsible for detecting and communicating messages to other immune cells in the immune cell population, directing other immune cells to attack the cancer cells

In fact, Ralph A. Cohn's discovery of dendritic cells and their underlying mechanism was the subject of a Nobel Prize in Physiology and Medicine on October 3, 2011. p>

In fact, Dr. Ralph Steinman was diagnosed with cancer in 2007. Dr. Steinman was diagnosed with pancreatic cancer in 2007, and using his research on the dendritic cell mechanism, Dr. Ralph immunotherapeutically treated himself, and he went on to survive for four years. Dr. Ralph's immunotherapy of himself used the method of culturing dendritic cells in vitro and then injecting them back into the body. At the same time, Japanese medical institutions were using a similar approach to immunotherapy for their patients.

Part.6 Immune cell therapy in Japan

Immune cell therapy in Japan includes a variety of treatments, including: αβ T cells, γδ T cells, DC vaccine (dendritic cell vaccine) carrying long-chain antigens, NKT cells, and NK cells. Among them, dendritic cells are recognized as the most effective and have the best therapeutic effect on solid tumors. In actual treatment, one or more mixed cell's are used for treatment according to each patient's individual situation.

The basic principle of ex vivo immune cell reflux is to recognize and guide the dendritic cells, which play a major role, and then use other aggressive immune cells to eradicate the cancer cells. Most of the people currently receiving immunotherapy by way of reflux are patients with intermediate to advanced cancers, and the immunotherapy can also be used in conjunction with other standard treatments, such as radiation, chemotherapy, and PD1. Information published so far suggests that there are virtually no side effects from this approach.

The method used by most medical institutions in Japan for immunotherapy is to grow dendritic cell vaccines (which utilize cancer antigens to enhance recognition of cancer cells) and other aggressive immune cells in vitro, and then inject them back into the body. The main mechanism is to culture the dendritic vaccine in vitro and activate an attacking immune cell (making it more aggressive.) Clinical treatment began in 2007, with a published clinical efficacy rate of about 50% (efficacy includes tumor disappearance, shrinkage, or lack of progression, depending on the type of cancer), and a treatment cycle of about 3 to 4 months***5-6 reinjections.

Part.7 ?Combination of PD1 and immunotherapy

There are immunotherapies such as cellular therapies, which increase the aggressiveness of immune cells, and blockade therapies, which disarm immunosuppression to maintain cell activity. In Japan, there are some immunocell therapy facilities that have adopted both of these therapies to carry out treatments at the same time.

Immune cell therapy ? This is a therapy that increases the ability of immune cells to attack cancer cells by activating a large number of dendritic cells, NK cells, and so on.

Feature ①: Increase the polyvalent cancer antigen to recognize foreign cells to improve the attacking efficiency, and the average effective rate is more than one times higher than that of chemotherapy.

Feature ②: almost no side effects.

Immune blocking therapy ? It is a therapy that blocks immunosuppressive points, such as PD1 agents, so that normal immune cells are active to fight back against cancer cells. The latest clinical statistics from abroad found its effective rate to be 20-30%; its side effects are not as strong as those of chemotherapy drugs, but it can cause inflammation.

Immunity combination therapy ? is the simultaneous use of immune cell therapy and immune blocking therapy. Combination therapy is a brand-new treatment approach, and there is every reason to expect that its therapeutic effects will probably be the mainstay of cancer treatment in the future. However, combination therapy requires the attending physician to have extensive experience in oncology and a deep understanding of immunology and its application to ensure patient safety first, and the clinical effectiveness has yet to be proved by data.

Part.8 ? Treatment examples of immunotherapy

Of the 191 patients (86 males and 105 females) treated at an immunotherapy facility in Japan, after the completion of 1 course of 6 treatments, cancer lesions were detected through the use of CT, MRI, and PET-CT to follow up before and after the treatments, and the treatment effectiveness rates were as follows (data from January 2015):

Determination Criteria

A determination: tumor disappearance, reduction of tumor markers, no signs of recurrence status.

Determination B: The size of the tumor and its metastatic status have not changed, and the tumor markers have decreased or remained unchanged. The quality of life is improved, and survival with cancer ****.

Determination C: the tumor is still gradually increasing in size and tumor markers are gradually rising after receiving treatment, but the deterioration has become slow and there is a life-prolonging effect.

D Judgment: Even after receiving treatment, the deterioration state still persists.

Treatment efficiency: 60% or more

A judgment: complete? Judgment A: complete or partial remission 24% + Judgment B: long-term unchanged 38%

※Treatment effectiveness: Treatment effectiveness is judged based on the RECIST guidelines, which are an international benchmark.

Treatment regimen of 191 patients

▲Immunotherapy alone (106 patients)

A judgment + B judgment (long-term unchanged): 57 patients (54%)

▲Patients treated with anticancer agents (85 patients)

A judgment + B judgment (long-term unchanged): 61 patients (72%)

Patients with immunotherapy alone (106 patients):

A judgment + B judgment (long-term unchanged):

Patients with immunotherapy (85 patients):

A judgment + B judgment (long-term unchanged): 61 patients (72%) )

※Disease stage and judgment

Detailed analysis of the disease stage (phase) of 191 patients: about 84%***159 of them were in stage IIIb or later.

Stage I: The tumor is small and the cancer has not spread to adjacent tissues. The cancer was judged to be early stage.

Stage II: Smaller tumor with spread but limited to surrounding lymph nodes and adjacent tissues.

Stage III: Progressive cancer with larger tumors that have spread to adjacent organs.

Stage IV: The tumor has metastasized to other organ states far away (distant metastasis).

Actual case 1.

Disease name: primary lung cancer with metastasis to the adrenal gland

Patient: 41 years old female

Therapy: dendritic cell vaccine + chemotherapy

Passage: primary lung cancer with metastasis to the right adrenal gland was detected in October, 2016, and CBDCA + TXT chemotherapy was started immediately. Simultaneously using 1 course

of dendritic cell vaccine, the primary lung foci shrunk by 78%, the adrenal gland was significantly shrunk, and the tumor markers were normal.

Actual case 2.

Disease name: pancreatic cancer stage IV, liver metastasis

Patient: 66 years old male

Therapy: dendritic cell vaccine

Procedure: found in September 2016, received 1 course of chemotherapy, then in March began to receive WT1, MUC-1, CA125 multivalent dendritic cell vaccine

treatment . Tumor marker DUPAN2 decreased from 25,300U/ml to 1,640U/ml. primary foci disappeared and metastases shrunk.

Warm tips:

At present, immune cell therapy cannot replace standard treatment (surgery, chemotherapy and radiotherapy). Patients need to combine their own conditions, and if they have some financial ability, they can receive regular standard treatment with the immune combination therapy to activate the immune system, prolong the survival period, and prevent the recurrence of cancer.